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R Muharam,1– 3 Anom Bowolaksono,1,4 Mila Maidarti,1– 3 Ririn Rahmala Febri,1 Kresna Mutia,1 Pritta Ameilia Iffanolida,1 Muhammad Ikhsan,1– 3 Kanadi Sumapraja,1– 3 Gita Pratama,1– 3 Achmad Kemal Harzif,1– 3 Andon Hestiantoro,1– 3 Budi Wiweko1– 3 1Human Reproduction, Infertility and Family Planning Research Center, Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia Jakarta, Jakarta, 10430, Indonesia; 2Division of Reproductive Endocrinology and Infertility Department of Obstetrics and Gynecology, Faculty of Medicine Universitas Indonesia, DKI Jakarta, 10430, Indonesia; 3Yasmin IVF Clinic, Dr. Cipto Mangunkusumo General Hospital, Jakarta, 10430, Indonesia; 4Cellular and Molecular Mechanisms in Biological System (CEMBIOS) Research Group, Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, Depok, 16424, IndonesiaCorrespondence: R Muharam, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology - Faculty of Medicine Universitas Indonesia, Jl. Diponegoro No. 71, Salemba, Jakarta Pusat, DKI Jakarta, 10430, Indonesia, Tel +62 3928720 / +62 816 1188027, Email rmuharam@yahoo.comPurpose: This study aimed to measure the correlation between miR-183 and gene expression that regulates apoptosis and adhesion mechanism that may be linked to the pathogenesis of endometriosis.Patients and Methods: Forty-four subjects, including 22 control subjects, participated in this study. We collected ectopic endometriosis and endometrial samples. For the control, the sample was taken from endometrial tissue through pipelle biopsy. RNA was extracted from all tissues using RNA mini kit, and the expression was assessed using quantitative-real time PCR. Relative mRNA and miRNA expression were presented using the formula of the Livak method. The data were statistically analyzed using GraphPad Prism 8.Results: The expression of Caspase-3, Survivin, Integrin β 1 (ITGB1), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) (adhesion- and apoptosis-related gene) were calculated using the relative expression method. We found significant differences in Caspase-3, Survivin, ITGB1, MMP-9, and TIMP-1 expression between ectopic endometriosis tissues of women with endometriosis compared to healthy endometrium. MMP-9, Survivin, and ITGB1 was significantly increased in the endometriosis group, while Caspase-3, TIMP-1, and miR-183 were significantly reduced in the endometriosis group. No correlation was found between the expression level of miR-183 and Caspase3, Survivin, ITGB1, and Cadherin in both tissue types.Conclusion: Despite the difference in expression levels of miR-183 and associated adhesion- and apoptosis-related genes, there was no significant association between miR-183 with specific adhesion and apoptosis genes in endometriosis tissue.Keywords: endometriosis, miR-183, MMP-9, TIMP1, apoptosis, antiapoptosis

Abstract Age-related osteoporosis is a prevalent bone metabolic disorder distinguished by an aberration in the equilibrium between bone formation and resorption. The reduction in the stemness of Bone Marrow Mesenchymal Stem Cells (BMSCs) plays a pivotal role in the onset of this ailment. Comprehending the molecular pathways that govern BMSCs stemness is imperative for delineating the etiology of age-related osteoporosis and devising efficacious treatment modalities. The study utilized single-cell RNA sequencing and miRNA sequencing to investigate the cellular heterogeneity and stemness of BMSCs. Through dual-luciferase reporter assays and functional experiments, the regulatory effect of miR-183 on CTNNB1 (β-catenin) was confirmed. Overexpression and knockdown studies were conducted to explore the impact of miR-183 and β-catenin on stemness-related transcription factors Oct4, Nanog, and Sox2. Cell proliferation assays and osteogenic differentiation experiments were carried out to validate the influence of miR-183 and β-catenin on the stemness properties of BMSCs. Single-cell analysis revealed that β-catenin is highly expressed in both high stemness clusters and terminal differentiation clusters of BMSCs. Overexpression of β-catenin upregulated stemness transcription factors, while its suppression had the opposite effect, indicating a dual regulatory role of β-catenin in maintaining BMSCs stemness and promoting bone differentiation. Furthermore, the confluence of miRNA sequencing analyses and predictions from online databases revealed miR-183 as a potential modulator of BMSCs stemness and a novel upstream regulator of β-catenin. The overexpression of miR-183 effectively diminished the stemness characteristics of BMSCs by suppressing β-catenin, whereas the inhibition of miR-183 augmented stemness. These outcomes align with the observed alterations in the expression levels and functional assessments of transcription factors associated with stemness. This study provides evidence for the essential involvement of β-catenin in preserving the stemness of BMSCs, as well as elucidating the molecular mechanism through which miR-183 selectively targets β-catenin to modulate stemness. These results underscore the potential of miR-183 and β-catenin as molecular targets for augmenting the stemness of BMSCs. This strategy is anticipated to facilitate the restoration of bone microarchitecture and facilitate bone tissue regeneration by addressing potential cellular dysfunctions, thereby presenting novel targets and perspectives for the management of age-related osteoporosis.

Age-related osteoporosis is a prevalent bone metabolic disorder distinguished by an aberration in the equilibrium between bone formation and resorption. The reduction in the stemness of Bone Marrow Mesenchymal Stem Cells (BMSCs) plays a pivotal role in the onset of this ailment. Comprehending the molecular pathways that govern BMSCs stemness is imperative for delineating the etiology of age-related osteoporosis and devising efficacious treatment modalities. The study utilized single-cell RNA sequencing and miRNA sequencing to investigate the cellular heterogeneity and stemness of BMSCs. Through dual-luciferase reporter assays and functional experiments, the regulatory effect of miR-183 on CTNNB1 (β-catenin) was confirmed. Overexpression and knockdown studies were conducted to explore the impact of miR-183 and β-catenin on stemness-related transcription factors Oct4, Nanog, and Sox2. Cell proliferation assays and osteogenic differentiation experiments were carried out to validate the influence of miR-183 and β-catenin on the stemness properties of BMSCs. Single-cell analysis revealed that β-catenin is highly expressed in both high stemness clusters and terminal differentiation clusters of BMSCs. Overexpression of β-catenin upregulated stemness transcription factors, while its suppression had the opposite effect, indicating a dual regulatory role of β-catenin in maintaining BMSCs stemness and promoting bone differentiation. Furthermore, the confluence of miRNA sequencing analyses and predictions from online databases revealed miR-183 as a potential modulator of BMSCs stemness and a novel upstream regulator of β-catenin. The overexpression of miR-183 effectively diminished the stemness characteristics of BMSCs by suppressing β-catenin, whereas the inhibition of miR-183 augmented stemness. These outcomes align with the observed alterations in the expression levels and functional assessments of transcription factors associated with stemness. This study provides evidence for the essential involvement of β-catenin in preserving the stemness of BMSCs, as well as elucidating the molecular mechanism through which miR-183 selectively targets β-catenin to modulate stemness. These results underscore the potential of miR-183 and β-catenin as molecular targets for augmenting the stemness of BMSCs. This strategy is anticipated to facilitate the restoration of bone microarchitecture and facilitate bone tissue regeneration by addressing potential cellular dysfunctions, thereby presenting novel targets and perspectives for the management of age-related osteoporosis. [ABSTRACT FROM AUTHOR]

Introduction: Accumulating evidence has proved that long non-coding RNAs (lncRNAs) are involved in progression of glioma. Nevertheless, the role of TUBA4B in glioma remains unclear. Material and methods: The expression of the target gene was measured by quantitative RT-PCR. The prognostic role of TUBA4B was analyzed by Meier survival analysis. Cell proliferation, colony formation, apoptosis, cell cycle, migration and invasion were detected by MTS, soft agar colony forming assay, flow cytometry, and transwell assay. The target interaction of the target gene was validated by the luciferase reporter assay, biotin pull-down assay, and RNA immunoprecipitation. Results: We found that the expression of TUBA4B was lower in glioma tissues and cells. Moreover, patients with a low TUBA4B expression level exhibited poorer prognosis than those with high TUBA4B expression. Meanwhile, ROC analysis revealed that TUBA4B had diagnostic value to distinguish tumor patients from the healthy population. Overexpression of TUBA4B prohibited the malignancy of glioma, such as inhibition of proliferation, decrease of colony formation, arrest of the cell cycle, decline of migration and invasion, and promotion of cell apoptosis. In addition, we found that TUBA4B directly interacted with miR-183 and negatively regulated the expression of miR-183. We also observed that SMAD4 was a downriver target of miR-183 and TUBA4B subsequently exerted its tumor-suppressive effects by coordinating the expression of SMAD4 in glioma. Conclusions: This study revealed for the first time that TUBA4B could be a tumor suppressor gene in glioma by adjustment of the TUBA4B/miR-183/SMAD4 axis, which may provide a useful prognostic biomarker and promising therapeutic target for glioma treatment. [ABSTRACT FROM AUTHOR]

Objective Exploring the influence of rapamycin on the progressing of hepatocellular carcinoma(HCC) in H-ras 12V transgenic mice. Methods The expression level of miRNA in liver tissue and peritumor tissue of transgenic mice was detected by high-throughput sequencing of miRNAs. Treatment of transgenic mice with rapamycin and the changes of tumor morphology were detected. The miR-183 expression levels were detected by RT-qPCR. The protein expression levels of mTOR, ERK and PDCD4, the downstream target gene of miR-183, were detected by Western blot. Results Compared with the peritumor tissue, the miR-183 expression in hepatocellular carcinoma tissue was increased significantly (P＜0.01). The protein expression levels of PDCD4 were decreased significantly(P＜0.05). Compared with the control group, after intervention with rapamycin, the counting of liver tumors decreased significantly(P＜0.05). The liver co-efficient decreased significantly(P＜0.05). The ERK phosphorylation increased significantly (P＜0.05). The miR-183 expression was decreased significantly (P＜0.05). The protein level of PDCD4 increased significantly (P＜0.05). Conclusions Rapamycin can alleviate hepatocellular carcinoma progression in H-ras 12V transgenic mice.

Copyright of Basic & Clinical Medicine is the property of Editorial Office of Basic & Clinical Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Ischemia–reperfusion (I/R) injury is a crucial factor causing liver injury in the clinic. Recent research has confirmed that human adipose‐derived stem cells (ADSCs) can differentiate into functional hepatocytes. However, the mechanism of the effects of ADSCs in the treatment of liver injury remains unclear. The characteristics of ADSCs were first identified, and exosome‐derived ADSCs were isolated and characterized. The function and mechanism of action of miR‐183 and arachidonate 5‐lipoxygenase (ALOX5) were investigated by functional experiments in HL‐7702 cells with I/R injury and in I/R rats. Our data disclosed that exosome release from ADSCs induced proliferation and inhibited apoptosis in HL‐7702 cells with I/R injury. The effect of miR‐183 was similar to that of exosomes derived from ADSCs. In addition, ALOX5, as a target gene of miR‐183, was involved in the related functions of miR‐183. Moreover, in vivo experiments confirmed that miR‐183 and exosomes from ADSCs could improve liver injury in rats and inhibit the MAPK and NF‐κB pathways. All of these findings demonstrate that exosomes derived from ADSCs have a significant protective effect on hepatic I/R injury by regulating the miR‐183/ALOX5 axis, which might provide a therapeutic strategy for liver injury. [ABSTRACT FROM AUTHOR]

Background & Aims: Today, cancer is considered as a major health problem and affects the health of society. Breast cancer is the second leading cause of cancer death in women after lung cancer. According to epidemiological studies, cancer is the second most common cause of death after cardiovascular disease worldwide and the third leading cause of death after cardiovascular disease and accidents in less developed countries. Cancer occurs as a result of uncontrolled cell division, which is the result of environmental factors and genetic disorders. The four key genes involved in cancer cell development include oncogenes, tumor suppressor genes, DNA repair genes, and programmed death genes. The prevalence of breast cancer varies from about 8 to 12 women in different communities. About 30% of all monogenic breast cancers are due to mutations in the BRCA breast cancer genes, which will eventually lead to breast cancer with a dominant inheritance pattern. Repair genes naturally make proteins and enzymes that repair damaged genes. When these genes are mutated, they cannot repair the defects of other genes. One of the repairing genes is BRCA-1 gene, which has a hereditary role in the production and growth of cancer cells in female breasts when it has a mutation. MicroRNAs are a group of short, single-stranded (between 19 and 23 nucleotides) and non-coding conserved RNAs that act as post-transcriptional regulators of gene expression in a wide range of animals, plants, and viruses. The FOXO1 gene is one of the targets of miR-183, which is involved in the maturation of lymphocytes, and increased expression of miR-183 in cancer patients will interfere with immune function. Studies on miR-183-3p in breast cancer have shown that this microRNA is a Tumor suppressor-mir (Ts-mir) that prevents tumor formation and differentiation and has an inhibitory role. Another feature is the inhibition of cell proliferation and metastasis and stops the cell cycle in the G1 stage. miR-183 can play a role in other cancers in addition to breast cancer, depending on the type of target and location of activity. The aim of this study was to evaluate the expression changes of miR-183 in nuclear nuclei of breast cancer patients. Methods: The study was performed on 60 samples including two groups of patients and healthy people. All actions and tests performed in this research and sampling have been approved by the work instructions of the ethics committee of Qom branch of the Azad University (ethics code: IR.IAU.QOM.REC.1397.010). Study steps include: extraction of peripheral blood mononuclear cells (PBMCs), extraction of RNA from PBMCs obtained from patients, design of specific primers for target genes, synthesis of cDNA from RNAs obtained, quality control of cDNA synthesized with Use of beta-actin and 5SrRNA housekeeping genes and ensure cDNA health, Real Time PCR to study changes in FOXO1 gene expression, changes in miR-183 and finally statistical analysis. In this study, the results obtained from Real-time PCR (Ct) were analyzed using LinReg software by examining the amount of fluorescence read by the device for each sample and the efficiency of each sample, the Ct of the reference gene and the target gene in both patient and healthy groups The data were then used and analyzed by Rest 2009 to determine whether the P-value was less than 0.05. Results: The results of analysis of data obtained from Real time-PCR show that the expression of FOXO1 gene in peripheral blood cells significantly decreases in samples of breast cancer patients compared to healthy individuals (P < 0.05). While in the expression of miR-183 gene, a significant increase was observed in the samples of people with breast cancer compared to the group of healthy people (P <0.001). Conclusion: Decreased expression of FOXO1 gene reduces the maturation of lymphocytes and this function weakens and suppresses the immune system, which results in the proliferation and differentiation of cancer cells and tumor spread, which can be used as a biomarker. Limitations of the study include the small number of patients, the lack of classification of patients based on markers such as Her2nue, BRCA-1 and other diagnostic markers. [ABSTRACT FROM AUTHOR]

Background: Lymph node metastasis (LNM) is a point that often, treatment is not effective in colorectal cancer (CRC). Clinical and pathologic markers of prognosis help clinicians in selecting patients for adjuvant therapy after surgical resection in CRC. MiR-183-5p has been demonstrated to play as an oncogene in CRC, although its biological role still remains unclear. The aim of this study was to evaluate the expression of miR-183-5p in CRC and its potential relevance to clinicopathological characteristics as a prognostic biomarker.Materials and Methods: In this case-control study, 33 CRC plasma samples at stage I-II-III, as well as plasma samples from 13 healthy controls, were collected. The relative expression levels of miR-183-5p in cancer and the normal samples were measured by quantitative real-time PCR. We analyzed their correlation with clinicopathological parameters and prognostic value.Results: Our results indicated that miR-183-5p was significantly overexpressed in CRC samples compared to healthy controls (P < 0.001) from a cutoff value of 3.9 with a sensitivity of 89% and a specificity of 91% and an AUC value of 0.74. Further analysis showed that a high plasma expression level of miR-183-5p was significantly associated with LNM and higher tumor/node/metastases stage (III) (P-value < 0.001).Conclusion: In conclusion, the overexpression of miR-183-5p is highly related to advanced clinical stage, LNM and poor prognosis of CRC, indicating that miR-183-5p may serve as a predictive biomarker for the prognosis or the aggressiveness of CRC. [ABSTRACT FROM AUTHOR]

Laryngeal cancer (LCa) is a prevalent malignant head and neck cancer with relatively unclear pathogenesis. A prior study has suggested that miR-183 differentially expressed in laryngeal-related malignancies, but its accurate role has not been fully ascertained in LCa. miR-183 expression in LCa tissues and cells was detected assisted by TCGA/GEO databases or qRT-PCR assay, relatively. Target genes of miR-183 were predicted via accessing to TargetScan website. Luciferase activity analysis was conducted to determine the relationship between miR-183 and its possible target. CCK-8, colony formation and transwell invasion and migration experiments were implemented to measure LCa cell viability, invasion and migration. Western blot assay was utilized to evaluate cell adhesion and EMT-related proteins expressions. The expression of miR-183 was expressed in LCa tissue samples and cells at higher levels than normal controls. Upregulation of miR-183 facilitated Hep-2 and TU212 cells viability, while miR-183 reduction inhibited the proliferative potential of Hep-2 and TU212 cells. TMSB4Y was determined as a possible target of miR-183, and its expression was decreased in LCa. LCa patients with low TMSB4Y expression had poorer outcomes relative to that with high TMSB4Y expression. TMSB4Y overturned the promoting impacts of miR-183 on the LCa cellular malignant behaviors, including cell proliferation, colonogenicity, invasion and migration. miR-183 overexpression inhibited cell adhesion through inhibiting TMSB4Y expression. Overall, all results elucidated that miR-183, as an oncogenic molecule in LCa, may be used to predict the prognosis of LCa patients by targeting TMSB4Y. [ABSTRACT FROM AUTHOR]

Abstract Background The expression of SIN3A is closely correlated with electroacupuncture (EA) treatment efficacy of scopolamine-induced amnesia (SIA), but its underlying mechanisms remain to be further explored. Methods Quantitative real-time PCR was performed to analyze the expression of candidate microRNAs (miRNAs) and SIN3A mRNA in a rat model of SIA. Western blot was carried out to evaluate the differential expression of SIN3A proteins under different circumstances. Luciferase assay was used to explore the inhibitory role of certain miRNAs in SIN3A expression. A novel object recognition (NOR) test was performed to assess the memory function of SIA rats undergoing EA treatment. Immunohistochemistry was carried out to evaluate the expression of SIN3A in the hippocampus of SIA rats. Results Rno-miR-183-5p, rno-miR-34c-3p and rno-miR-210-3p were significantly up-regulated in SIA rats treated with EA. In addition, rno-miR-183-5p and rno-miR-210-3p exerted an inhibitory effect on SIN3A expression. EA treatment of SIA rats effectively restored the dysregulated expression of rno-miR-183-5p, rno-miR-210-3p and SIN3A. EA treatment also promoted the inhibited expression of neuronal IEGs including Arc, Egr1, Homer1 and Narp in the hippocampus of SIA rats. Accordingly, the NOR test also confirmed the effect of EA treatment on the improvement of memory in SIA rats. Conclusion In summary, the findings of this study demonstrated that scopolamine-induced amnesia was associated with downregulated expression of miR-210/miR-183 and upregulated expression of SIN3A. Furthermore, treatment with EA alleviated scopolamine-induced amnesia in rats and was associated with upregulated expression of miR-210/miR-183 and downregulated expression of SIN3A.

Objective To investigate the protective effect of β-caryophyllene (BCP) against ischemic stroke injury in mice and clarify whether such protective effects are associated with miR-183 and nuclear factor-κB (NF-κB) expression. Methods Ninety male C57BL/6 mice were randomized equally into 3 groups, namely the sham-operated group, ischemia-reperfusion (I/R) model group, and BCP (72 mg/kg) pretreatment group. The mice in the latter 2 groups were subjected to middle cerebral artery occlusion for 60 min followed by reperfusion for 24 h. The neurological deficits and infarct volume of the mice were measured, and the pathological changes in the brain tissues were observed using HE and Nissl staining. The expression of miR-183, NF-κB, p-NF-κB, interleukin-1β (IL-1β), and IL-6 in the brain were detected, and the targeting relationship between miR-183 and NF-κB was determined. In the in vitro experiment, the cortical neurons isolated from the brain of neonatal mice were divided into normal group, oxygen-glucose deprivation (OGD) group, and OGD group with 10 μmol/L BCP pretreatment. Immunofluorescence assay was employed for morphological observation of the neurons, and the cell injury was assessed with lactate dehydrogenase (LDH) leakage assay. The expression levels of miR-183, IL-1β, IL-6 and NF-κB in the neurons were measured. Results In the mouse models of ischemic stroke, BCP pretreatment significantly improved neurologic deficit score, reduced the infarct volume, lessened pathological changes of the brain tissue, and decreased the number of Nissl-positive cells in the cortex (P < 0.05). BCP pretreatment significantly upregulated the expression of miR-183 in the brain tissues of the mice (P < 0.05). In the in vitro experiment, BCP pretreatment produced obvious protective effect on neurons and significantly lowered neuronal death rate following OGD (P < 0.05). BCP treatment significantly upregulated the expression of miR-183, inhibited NF-κB activation and lowered the expressions of inflammatory factors in the neurons (P < 0.05). Conclusion BCP protects the brain tissues against ischemic stroke injury by upregulating the expression of miR-183, which inhibits NF-κB activation and lowers the release of inflammatory factors to alleviate inflammation in the brain.

BACKGROUND MicroRNAs serve as important regulators of the pathogenesis of cardiac hypertrophy. Among them, miR-183 is well documented as a novel tumor suppressor in previous studies, whereas it exhibits a downregulated expression in cardiac hypertrophy recently. The present study was aimed to examine the effect of miR-183 on cardiomyocytes hypertrophy. METHODS Angiotensin II (Ang II) was used for establishment of cardiac hypertrophy model in vitro. Neonatal rat ventricular cardiomyocytes transfected with miR-183 mimic or negative control were further utilized for the phenotype analysis. Moreover, the bioinformatics analysis and luciferase reporter assays were used for exploring the potential target of miR-183 in cardiomyocytes. RESULTS We observed a significant decreased expression of miR-183 in hypertrophic cardiomyocytes. Overexpression of miR-183 significantly attenuated the cardiomyocytes size morphologically and prohypertrophic genes expression. Moreover, we demonstrated that TIAM1 was a direct target gene of miR-183 verified by bioinformatics analysis and luciferase reporter assays, which showed a decreased mRNA and protein expression in the cardiomyocytes transfected with miR-183 upon Ang II stimulation. Additionally, the downregulated TIAM1 expression was required for the attenuated effect of miR-183 on cardiomyocytes hypertrophy. CONCLUSIONS Taken together, these evidences indicated that miR-183 acted as a cardioprotective regulator for the development of cardiomyocytes hypertrophy via directly regulation of TIAM1. [ABSTRACT FROM AUTHOR]

microRNAs associate with Argonaute proteins, forming the microRNA-induced silencing complex (miRISC), to repress target gene expression post-transcriptionally. Although microRNAs are critical regulators in mammalian cell differentiation, our understanding of how microRNA machinery, such as the miRISC, are regulated during development is still limited. We previously showed that repressing the production of one Argonaute protein, Ago2, by Trim71 is important for mouse embryonic stem cells (mESCs) self-renewal (Liu et al., 2021). Here, we show that among the four Argonaute proteins in mammals, Ago2 is the major developmentally regulated Argonaute protein in mESCs. Moreover, in pluripotency, besides the Trim71-mediated regulation of Ago2 (Liu et al., 2021), Mir182/Mir183 also repress Ago2. Specific inhibition of this microRNA-mediated repression results in stemness defects and accelerated differentiation through the let-7 microRNA pathway. These results reveal a microRNA-mediated regulatory circuit on microRNA machinery that is critical to maintaining pluripotency.

Multidrug resistance (MDR) is the biggest challenge in cancer therapy. In this study, we explored the molecular mechanism of MDR in human liver cancer and explored the related diagnostic and prognostic values of the targeted genes in patients with hepatocellular carcinoma. We constructed a multidrug-resistant liver cancer cell line, HepG2/Dox, using the parental subline HepG2. The (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay was used to test the viability of the liver cancer cells. Western blotting was performed to test the expression of ABCB1, β-catenin, and β-actin. Luciferase assays were performed to confirm the relationship between miR-381 and its target genes. The diagnostic and prognostic values of target genes were analyzed using publicly available data from The Cancer Genome Atlas. The Mann–Whitney U test and logistic regression were performed to evaluate the association between ABCB1 or CTNNB1 expression and clinical features in patients with liver hepatocellular carcinoma (LIHC). Finally, Kaplan-Meier and Cox regression analyses were performed to test the effect of ABCB1 or CTNNB1 expression on the overall survival of patients with LIHC. ABCB1 expression was upregulated in HepG2/Dox cells. ABCB1 was found to be a direct target of hsa-miR-381 and was negatively regulated by has-miR-381. Moreover, hsa-miR-381 directly targeted the CTNNB1 3′ UTR and decreased the luciferase activity of CTNNB1. Transfection with miR-183 partially reversed chemotherapeutic drug resistance by downregulating the expression of ABCB1 and CTNNB1 in HepG2/Dox cells. Spearman's analysis results showed that CTNNB1 and ABCB1 were positively correlated in patients with liver cancer, and increased CTNNB1 and ABCB1 expression occurred in patients with liver cancer. High expression of ABCB1 and CTNNB1 indicated poor prognosis in patients with liver cancer; however, neither ABCB1 nor CTNNB1 expression was an independent diagnostic factor in patients with LIHC. Overexpression of hsa-miR-381 partially reversed the MDR of HepG2 cells by directly targeting and negatively regulating the expression of CTTNB1 and ABCB1. Moreover, high expression of ABCB1 or CTNNB1 indicated poor prognosis in patients with liver cancer. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Cancer Biotherapy is the property of Editorial Office of Chinese Journal of Cancer Biotherapy and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Chuanwu Cao,* Shilong Han,* Yifeng Yuan, Yongfa Wu, Weishuai Lian, Xiaojun Zhang, Long Pan, Maoquan Li Department of Interventional and Vascular Surgery, Tenth People’s Hospital of Tongji University, Shanghai 200072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Maoquan LiDepartment of Interventional and Vascular Surgery, Tenth People’s Hospital of Tongji University, 301 Middle Yan Chang Road, Shanghai 200072, People’s Republic of ChinaTel +86-021-66313506Email cjr.limaoquan@vip.163.comBackground: Circular RNAs are implicated in a variety of cancers. This investigation found that hsa_circ_0000291 expression was upregulated in gastric cancer (GC) cell lines, yet its role in GC has not yet been reported.Objective: To explore the effects of hsa_circ_0000291 on GC cell proliferation and invasion.Materials and methods: In the current research, we used the gastric cancer cell lines MGC803 and MKN-28 to study hsa_circ_0000291 function. The relationship between hsa_circ_0000291, miR-183 and ITGB1 was analyzed by firefly luciferase analysis and Western blots, and qRT-PCR approaches were used for protein and gene expression analysis, respectively. Tumor growth and metastasis were determined in nude mice xenografts using MKN-28 cells, with or without hsa_circ_000r0291 downregulation.Results: Our data showed that hsa_circ_0000291 was upregulated in GC cell lines, whereas hsa_circ_0000291 silencing suppressed cell metastasis and proliferation in in vivo and in vitro studies. Our results showed that the downregulation of hsa_circ_0000291 suppressed integrin beta 1 (ITGB1) expression via miR-183 “sponging,” which was validated by rescue experiments using the luciferase reporter assay. Our observations suggested that hsa_circ_0000291 silencing suppressed the aggressive, metastatic GC phenotype.Conclusion: Taken together, hsa_circ_0000291 knockdown inhibited GC cell metastasis and growth by regulating the miR-183/ITGB1 axis. Importantly, this approach could provide a therapy target and potential biomarker for the diagnosis and treatment of GC.Keywords: hsa_circ_0000291, miR-183, integrin beta 1, proliferation and migration, gastric cancer

Background. Increasing radiosensitivity of cancer cells can enhance the efficacy of cervical cancer treatment. Objectives. This study evaluated the potential roles and mechanism of baicalein in regulating the radiosensitivity of cervical cancer cells in vitro. Materials and methods. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to assess miR-183 expression in End1/E6E7 cells, Hela cells and Hela cells irradiated with X-ray (0 Gy, 1 Gy, 3 Gy, 5 Gy, and 10 Gy). Cell Counting Kit-8 (CCK-8) method measured cell viability of Hela cells after miR-183 regulation, baicalein or RO8191 treatment. Apoptosis rates were detected using flow cytometry. Thereafter, expression of Bcl-2, Bax and caspase-3 RNA was also detected through RT-qPCR. Protein concentrations of E-cadherin, N-cadherin, Vimentin in epithelial-mesenchymal transition (EMT), phospho-JAK2/STAT3, and total Janus kinase 2/signal transducer and activator of transcription 3 STAT3 (JAK2/STAT3) were examined using enzyme-linked immunosorbent assay (ELISA) methods. RO8191, a JAK2/STAT3 activator, was used to activate the JAK2/STAT3 signaling pathway. Results. The miR-183 expression was significantly lower in Hela cells compared to End1/E6E7 cells. Following upregulation of miR-183 in Hela cells, cell viability was inhibited while apoptosis was promoted. Moreover, EMT was inhibited after miR-183 over-expression. X-ray treatment markedly reduced the cell survival rate and increased miR-183 RNA expression. Baicalein treatment severely reduced the cell viability of 10-Gy X-rayirradiated Hela cells, partially reversing the effect of miR-183, and also increased apoptosis and prevented EMT in irradiated cells. Y1007/8 in JAK2 and tyrosine (Tyr) residue 705 of STAT3 were phosphorylated, resulting in high expression of JAK2/STAT3, which was decreased by irradiation and baicalein treatment. RO8191 activated JAK2/STAT3 signaling, promoted cell viability and EMT, and inhibited cell apoptosis, while baicalein partly reversed the functions of RO8191. Conclusions. Baicalein inhibited cell viability and EMT, and induced cell apoptosis of Hela cells, through upregulating miR-183 via inactivation of the JAK2/STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

Pre‐eclampsia (PE) is a major cause of maternal and perinatal death. Previous research has indicated the role of histone deacetylase 2 (HDAC2) in the pathogenesis of PE but the relevant molecular mechanisms are unknown. However, there is hitherto little information concerning the molecular mechanism behind HDAC2 in PE. Herein, we hypothesized that HDAC2 promotes trophoblast cell proliferation and this requires the involvement of microRNA‐183 (miR‐183), forkhead box protein A1 (FOXA1), and interleukin 8 (IL‐8). We collected placental specimens from 30 PE affected and 30 normal pregnant women. HDAC2 and FOXA1 were poorly expressed while miR‐183 and IL‐8 were highly expressed in placental tissues in PE. In vitro, HDAC2 overexpression enhanced the proliferation, migration, and invasion of human trophoblast cells HTR‐8/SVNEO. HDAC2 inhibited the expression of miR‐183 by diminishing H4 acetylation in the miR‐183 promoter region. miR‐183 inhibition by its specific inhibitor increased the expression of FOXA1 and thus enhanced HTR‐8/SVNEO cell proliferation, migration, and invasion. FOXA1, a transcriptional factor, enhanced HTR‐8/SVNEO cell proliferation, migration, and invasion by inhibiting the transcription of IL‐8. We also observed HDAC2 knockdown was lost upon FOXA1 overexpression, suggesting that HDAC2 could promote HTR‐8/SVNEO proliferation, migration, and invasion through the miR‐183/FOXA1/IL‐8 pathway. In summary, the results highlighted the role of the HDAC2/miR‐183/FOXA1/IL‐8 pathway in PE pathogenesis and thus suggest a novel molecular target for PE. [ABSTRACT FROM AUTHOR]

Background: Medullary thyroid cancer (MTC) accounts for 5%–10% of all thyroid cancers, but causes 13% of all thyroid cancer related deaths. MicroRNAs (miRs) have key functions in the development and progression of MTC. Altered expression of some miRs has been reported in many human cancers, including Thyroid cancer. Therefore, we aimed to analyze the expression of miR-154, miR-183 and miR-127 in MTC tumor tissues. Methods: In this case-control study, 15 MTC Formalin-fixed, paraffin-embedded (FFPE) tissue samples and 15 adjacent normal thyroid FFPE tissues, as a control group, were collected from Taleghani, and Loghman Hakim Hospitals, Tehran, Iran since 2005 till 2015. After RNA extraction and cDNA synthesis, the expression of miR-127, miR-154 and miR-183 was measured by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Results: Our data showed a significant increase in the expression of miR-127 in MTC samples in comparison with the control group (P

The microRNA miR-96 is important for hearing, as point mutations in humans and mice result in dominant progressive hearing loss. Mir96 is expressed in sensory cells along with Mir182 and Mir183, but the roles of these closely-linked microRNAs are as yet unknown. Here, we analyse mice carrying null alleles of Mir182, and of Mir183 and Mir96 together to investigate their roles in hearing. We found that Mir183/96 heterozygous mice had normal hearing and homozygotes were completely deaf with abnormal hair cell stereocilia bundles and reduced numbers of inner hair cell synapses at 4 weeks of age. Mir182 knockout mice developed normal hearing then exhibited progressive hearing loss. Our transcriptional analyses revealed significant changes in a range of other genes, but surprisingly there were fewer genes with altered expression in the organ of Corti of Mir183/96 null mice compared with our previous findings in Mir96Dmdo mutants, which have a point mutation in the miR-96 seed region. This suggests that the more-severe phenotype of Mir96Dmdo mutants compared with Mir183/96 mutants, including progressive hearing loss in Mir96Dmdo heterozygotes, is likely to be mediated by the gain of novel target genes in addition to the loss of its normal targets. We propose three mechanisms of action of mutant miRNAs: loss of targets that are normally completely repressed, loss of targets for which transcription is normally buffered by the miRNA, and gain of novel targets. Any of these mechanisms could lead to a partial loss of a robust cellular identity and consequent dysfunction.

MicroRNAs (miRNAs) are important regulators of gene expression. These small, non-coding RNAs post-transcriptionally silence messenger RNAs (mRNAs) in a sequence-specific manner. In this way, miRNAs control important regulatory functions, also in the retina. If dysregulated, these molecules are involved in several retinal pathologies. For example, several miRNAs have been linked to essential photoreceptor functions, including light sensitivity, synaptic transmission, and modulation of inflammatory responses. Mechanistic miRNA knockout and knockdown studies further linked their functions to degenerative retinal diseases. Of note, the type and timing of genetic manipulation before, during, or after retinal development, is important when studying specific miRNA knockout effects. Within this review, we focus on miR-124 and the miR-183/96/182 cluster, which have assigned functions in photoreceptors in health and disease. As a single miRNA can regulate hundreds of mRNAs, we will also discuss the experimental validation and manipulation approaches to study complex miRNA/mRNA regulatory networks. Revealing these networks is essential to understand retinal pathologies and to harness miRNAs as precise therapeutic and diagnostic tools to stabilize the photoreceptors’ transcriptomes and, thereby, function.

Embryo implantation plays a decisive role in pregnancy. While in the process of implantation, microRNA (miRNA) is an important regulatory factor in the post transcriptional level. However, the role of many miRNAs in embryo implantation remained unknown. In this study, microRNA-183 (miR-183) was found differentially expressed in mouse uterus during implantation. In vivo treatment of miR-183 agomir in the uterine horn before implantation could eliminate the number of implantation site. The localization of miR-183 in mouse uteri gradually changed from epithelial to stromal layer in early pregnancy. Mice implantation models demonstrated that the decrease of miR-183 was mainly caused by maternal factors. Loss and gain function of miR-183 in endometrial cell lines showed that miR-183 could inhibit cell migration, invasion and apoptosis. MiR-183 could inhibit embryo implantation by binding Heparin-Binding EGF-like growth factor (Hbegf) and Laminin gamma one (Lamc1), which were key genes in embryo apposition and penetration. All these evidences indicate that miR-183 plays an important role during embryo implantation. This study provides new insights into the functions of miR-183 during embryo implantation and the development of contraceptive drugs in early pregnancy. • MiR-183 was down regulated in mouse uterus during early pregnancy. • MiR-183 inhibited migration, invasion and apoptosis in Ishikawa cells. • Hbegf and Lamc1 were the target genes of miR-183. • MiR-183 was involved in the successful pregnancy during the process of implantation. [ABSTRACT FROM AUTHOR]

Background: As an important member of platinum-based chemotherapeutic drugs, cisplatin is effective and is commonly used in the treatment of esophageal cancer. However, repeated use of cisplatin usually causes severe side-effects on patients. Novel approaches should be explored to increase the sensitivity of cancer cells to cisplatin. Methods: The expression level of miR-183 in esophageal cancer tissues and cell lines was measured by quantitative reverse transcriptase real-time PCR (qRT-PCR). The sensitivity of EC cell lines to cisplatin was evaluated by CCK-8 assay and flow cytometry. Luciferase reporter assay was used to confirm the association between miR-183 and FOXO1. The apoptosis pathway of EC cells was tested by Western blot assay. Results: The expression level of miR-183 was increased in esophageal cancer patients' tumor tissues and esophageal cancer cell lines. However, knockdown of miR-183 was found to enhance the effect of cisplatin on inducing the apoptotic cell death of esophageal cancer cells. In the mechanism research, we proved that FOXO1 was the target of miR-183 in esophageal cancer cells. Inhibition of miR-183 increased the expression of FOXO1 to promote the expression of Bim and Noxa. As Bim and Noxa acted as key pro-apoptotic proteins in mitochondrial apoptosis, inhibition of miR-183 enhanced the cisplatin-induced apoptosis pathway in esophageal cancer. Conclusion: Knockdown of miR-183 enhanced the cisplatin-induced apoptosis in esophageal cancer through an increase of FOXO1 expression. [ABSTRACT FROM AUTHOR]

Objective To study the expression and diagnostic value of plasma miR-145 and miR-183 in children with lupus nephritis (LN). Methods A total of 92 children with LN who were admitted from January 2016 to May 2019 were enrolled as the LN group, among whom 17 had type II LN, 15 had type III LN, 36 had type IV LN, 18 had type V LN, and 6 had type VI LN. Forty healthy children who underwent physical examination were enrolled as the healthy control group. According to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the 92 children with LN were further divided into a stable LN group with 34 children (SLEDAI score <10) and an active LN group with 58 children (SLEDAI score ≥10). RT-PCR was used to measure the expression of miR-145 and miR-183 in plasma. The receiver operating characteristic (ROC) curve was used to analyze the value of plasma miR-145, miR-183, and anti-dsDNA antibody in the diagnosis of LN. Pearson correlation analysis was used to investigate the correlation of the expression levels of miR-145 and miR-183 in plasma with laboratory markers. Results The LN, active LN, and stable LN groups had significantly higher levels of anti-dsDNA antibody, C-reactive protein, serum creatinine (Scr), and blood urea nitrogen (BUN) than the control group (P<0.05). The active LN group had significantly higher SLEDAI score, anti-dsDNA antibody, Scr, and BUN than the stable LN group (P<0.05). The LN, active LN, and stable LN groups had significantly lower levels of complement C3, complement C4, and serum albumin (Alb) than the control group (P<0.05). The active LN group had a significantly lower level of Alb than the stable LN group (P<0.05). The LN, active LN, and stable LN groups had significantly lower plasma levels of miR-145 and miR-183 than the control group (P<0.01). The active LN group had significantly lower plasma levels of miR-145 and miR-183 than the stable LN group (P<0.01). The children with difference types of LN had significantly lower plasma levels of miR-145 and miR-183 than the control group (P<0.01), and the type V-VI group and the type IV group had significantly lower plasma levels of miR-145 and miR-183 than the type II-III group (P<0.01). The ROC curve analysis showed that the optimal cut-off values of plasma miR-145, miR-183, and anti-dsDNA antibody were 1.05, 0.62, and 186.30 IU/mL respectively, in the diagnosis of LN, and the combination of these three indices had the largest area under the ROC curve of 0.896 (95%CI: 0.835-0.955), with a sensitivity of 90.5% and a specificity of 84.2%. In the children with LN, the plasma levels of miR-145 and miR- 183 were negatively correlated with SLEDAI score, anti-dsDNA antibody, Scr, and BUN (P<0.05) and were positively correlated with complement C3, complement C4, and Alb (P<0.05). Conclusions There are significant reductions in the expression levels of miR-145 and miR-183 in plasma in children with LN, which are correlated with the activity level and pathological typing of LN. Combined measurement of miR-145, miR-183, and anti-dsDNA antibody has a high value in the diagnosis of LN. [ABSTRACT FROM AUTHOR]

MiR-183 is a tumor onco-miR and has been shown by our previous studies to be overexpressed in esophageal squamous cell carcinomas (ESCCs). In this study, we sought to determine the possible mechanisms of miR-183 in ESCC. In our study, cell migration and invasion, real-time PCR, Western blot, and chromatin immunoprecipitation (ChIP) assays were used to explore the mechanism of miR-183 in three ESCC cell lines. We found several potential transcription factors, including c-Jun, by bioinformatics methods. Using a ChIP assay, we identified that c-Jun binds to the promoter region of pre-miR-183 and that upregulated c-Jun expression is related to increased expression of miR-183. We found that downregulation of miR-183 significantly reduced the cell invasiveness and migration of ESCC cells, whereas upregulation of miR-183 via a mimic increased the cell migration and invasion of ESCC cells. We further discovered one direct miR-183 target gene, Smad4, which has been implicated in invasion and metastasis. Furthermore, miR-183 promoted epithelial-mesenchymal transition (EMT), which is involved in the invasion and migration of ESCC cells. Dysregulation of miR-183 has an important role in tumor growth and invasion because miR-183 targets Smad4. Therefore, suppression of miR-183 may provide a potential approach for treatment. [ABSTRACT FROM AUTHOR]

The TREK family of leak potassium channels has been found to play critical roles in nociception, sensitivity to general anaesthetics, neuroprotection, and memory. The three members of the family, TREK1, TREK2 and TRAAK establish the resting potential and modify the duration, frequency and amplitude of action potentials. Despite their apparent importance, the repertoire of regulatory interactions utilized by cells to control their expression is poorly understood. Herein, the contribution of miRNAs in the regulation of their post-transcriptional gene expression has been examined. Using different assays, miR-124 and to a lesser extent miR-128 and miR-183 were found to reduce TREK1 and TREK2 levels through specific binding to their 3ʹUTRs. In contrast, miR-9 which was predicted to bind to TRAAK 3ʹUTR, did not alter its expression. Expression of miR-124, miR-128 and miR-183 was found to mirror that of Trek1 and Trek2 mRNAs during brain development. Moreover, application of proinflammatory mediators in dorsal root ganglion (DRG) neurons revealed an inverse correlation between miR-124 and Trek1 and Trek2 mRNA expression. Voltage clamp recordings of TREK2-mediated currents showed that miR-124 reduced the sensitivity of TREK2-expressing cells to non-aversive warmth stimulation. Overall, these findings reveal a significant regulatory mechanism by which TREK1 and TREK2 expression and hence activity are controlled in neurons and uncover new druggable targets for analgesia and neuroprotection. Abbreviations: microRNA: miRNA; UTR: untranslated region; K2p channels: two-pore domain K+channels; DRG: dorsal root ganglion; CNS: central nervous system; FBS: fetal bovine serum; TuD: Tough Decoy; TREK: tandem P-domain weak inward rectifying K+ (TWIK)-related K+ channel 1; TRAAK: TWIK-related arachidonic acid K+. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is the most common and aggressive cancer of the digestive system and poses a serious threat to human health. Since genes do not work alone, our aim was to elucidate the potential network of mRNAs and noncoding RNAs (ncRNAs) in this study. Methods: Transcriptome data of GC were obtained from TCGA. R and Perl were used to obtain the differentially expressed RNAs and construct a competing endogenous RNA (ceRNA) regulatory network. To investigate the biological functions of differentially expressed RNAs, loss-of-function and gain-of-function experiments were performed. Real-time PCR (RT-qPCR), western blot analysis, dual-luciferase reporter assays and fluorescence in situ hybridization were conducted to explore the underlying mechanisms of competitive endogenous RNAs (ceRNAs). Results: Based on TCGA data and bioinformatics analysis, we identified the LINC00163/miR-183/A-Kinase Anchoring Protein 12 (AKAP12) axis. We observed that AKAP12 was weakly expressed in GC and suppressed invasion and metastasis in GC cells, which could be abolished by miR-183. In addition, LINC00163 can be used as a ceRNA to inhibit the expression of miR-183, thus enhancing the anticancer effect of AKAP12. Conclusion: Our results demonstrated that weak LINC00163 expression in GC can sponge miR-183 to promote AKAP12. We established that the LINC00163/miR-183/AKAP12 axis plays an important role in GC invasion and metastasis and may be a potential biomarker and target for GC treatment. [ABSTRACT FROM AUTHOR]

Many studies have verified that microRNAs contribute a lot to neuropathic pain progression. Furthermore, nerve‐related inflammatory cytokines play vital roles in neuropathic pain progression. miR‐183 has been identified to have a common relationship with multiple pathological diseases. However, the potential effects of miR‐183 in the process of neuropathic pain remain undetermined. Therefore, we performed the current study with the purpose of finding the functions of miR‐183 in neuropathic pain progression using a chronic sciatic nerve injury (CCI) rat model. We demonstrated that miR‐183 expression levels were evidently reduced in CCI rats in contrast with the control group. Overexpression of miR‐183 produced significant relief of mechanical hyperalgesia, as well as thermal hyperalgesia in CCI rats. Furthermore, neuropathic pain‐correlated inflammatory cytokine expression levels containing interleukin‐6 (IL‐6) and interleukin‐1β (IL‐1β), cyclooxygenase‐2 (COX‐2) were obviously inhibited by upregulation of miR‐183. Meanwhile, dual‐luciferase reporter assays showed MAP3K4 was a direct downstream gene of miR‐183. The expression levels of MAP3K4 were modulated by the increased miR‐183 negatively, which lead to the downregulation of IL‐6, IL‐1β, and COX‐2, and then reduced neuropathic pain progression, respectively. Overall, our study pointed out that miR‐183 was a part of the negative regulator which could relieve neuropathic pain by targeting MAP3K4. Thus it may provide a new clinical treatment for neuropathic pain patients clinical therapy. [ABSTRACT FROM AUTHOR]

Prostate cancer is a major health problem worldwide. MiR-183 is an oncomiR and a candidate biomarker in prostate cancer, affecting various pathways responsible for disease initiation and progression. We sought to discover the most relevant processes controlled by miR-183 through an unbiased transcriptomic approach using prostate cell lines and patient tissues to identify miR-183 responsive genes and pathways. Gain of function experiments, reporter gene assays, and transcript and protein measurements were conducted to validate predicted functional effects and protein mediators. A total of 135 candidate miR-183 target genes overrepresenting cell adhesion terms were inferred from the integrated transcriptomic analysis. Cell attachment, spreading assays and focal adhesion quantification of miR-183-overexpressing cells confirmed the predicted reduction in cell adhesion. ITGB1 was validated as a major target of repression by miR-183 as well as a mediator of cell adhesion in response to miR-183. The reporter gene assay and PAR-CLIP read mapping suggest that ITGB1 may be a direct target of miR-183. The negative correlation between miR-183 and ITGB1 expression in prostate cancer cohorts supports their interaction in the clinical set. Overall, cell adhesion was uncovered as a major pathway controlled by miR-183 in prostate cancer, and ITGB1 was identified as a relevant mediator of this effect.

Background/Aims: Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms which arise from pancreatic islet cells. Recently, lncRNA MEG3 has been reported as a tumor suppressor in variety cancers. This study aimed to reveal the functional effects of MEG3 on pNETs which has not been uncovered previously. Methods: The expression of MEG3, miR-183, and BRI3 in BON1 cells were altered by transfection with their specific vectors/shRNA, or mimic/inhibitor. Thereafter, cell viability, apoptosis, the protein expressions of cell cycle related factors, and apoptosis associated factors, as well as cell migration and invasion were respectively assessed by typan blue staining, flow cytometry, western blotting, and transwell assay. Results: MEG3 was low expressed in BON1 and QGP-1 cells, when compared to three normal cell lines (HEK293, CCL-153, and EC-304). MEG3 overexpression decreased BON1 cells viability, invasion, migration, but significantly induced apoptosis. miR-183 was a direct target of MEG3, and miR-183 up-regulation abolished the anti-growth and anti-metastasis effects of MEG3 overexpression on BON1 cells. Moreover, BRI3 was a target of miR-183, and BRI3 exhibited a tumor-promoting role possibly via activation of p38/ERK/AKT and Wnt/β-Catenin signaling in BON1 cells. Conclusion: This study demonstrated a tumor suppressive effect of MEG3 in BON1 cells that suppresses tumor cells growth and metastasis. A novel regulatory mechanism has been revealed that modulation of MEG3/miR-183/BRI3 axis may be pivotal in pNET.

Gastric cancer (GC) remains to be a familiar malignant tumor with poor prognosis and daunting impacts on global health. We planned to grab the latent impacts of microRNA-183 in regulating cell autophagy, thus to clarify its possible regulatory principle in GC. The miR-183 level in GC tissues and cell lines was investigated. The impacts of miR-183 dysregulation on cell biological performances including viability, apoptosis and autophagy of GC cell lines including SGC-7901 were detected. Also, cells were disposed with 3-methyladenine (3-MA, an autophagy inhibition) before dysregulation of miR-183 to further investigate the correlation between cell autophagy and viability or apoptosis. Furthermore, the regulatory mechanisms between miR-183 and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), silent mating type information regulation 1 (SIRT1) or PI3K/AKT/mTOR pathway were explored. miR-183 was under-expressed both in GC tissues and in cell lines. miR-183 mimic alone depressed SGC-7901 cell viability and enhanced cell apoptosis and autophagy, whereas miR-183 inhibitor exhibited opposite effects. Moreover, the impacts of miR-183 on SGC-7901 cell viability and apoptosis were mediated by affecting the activation of autophagy. Our results indicate that miR-183 is under-expressed in GC cells and depression of miR-183 may enhance GC cell viability and inhibit cell apoptosis by affecting the activation of cell autophagy. MALAT1-miR-183-SIRT1 axis and PI3K/AKT/mTOR pathway may be mechanisms to mediate autophagy in GC. miR-183 may serve as a towardly therapeutic target for GC. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) play a vital role in the occurrence and development of many human diseases, including systemic lupus erythematosus (SLE). SLE is an autoimmune disease characterized by the production of autoantibodies against nuclear antigens and multiorgan involvement. Study of miRNAs involved in SLE provides new insights into the pathogenesis of SLE and might lead to the identification of new therapeutic interventions. The aim of this study was to investigate the effect of miR‐183 injection on the progression of SLE by using MRL/lpr mouse model. The expression levels of miR‐183 and mTOR mRNA were detected by quantitative real‐time PCR assay. The effect of miR‐183 on the course of spontaneous disease progression in the MRL/lpr mice was examined by intraperitoneal injection of miR‐183 into mice and followed by monitoring lifespan, anti‐dsDNA antibody levels, urinary albumin levels, blood urea nitrogen (BUN) levels, and Tregs and Th17 cell population. We found that miR‐183 injection resulted in reduction of anti‐DNA antibody and immune complex component levels, restoration of Tregs and Th17 cell population and prolongation of survival. Our findings suggest that miR‐183 injection may serve as an effective therapeutic treatment for delaying or easing pathologic features of SLE. [ABSTRACT FROM AUTHOR]

Purpose: Hepatocellular carcinoma (HCC) is the most common malignant tumor of liver cells. Researchers have reported that cancer susceptibility candidate 2 (CASC2), a long non-coding RNA, is down-regulated in various cancers, including HCC. Our study aimed to investigate the molecular mechanism(s) of CASC2 in HCC. Materials and Methods: Real-time quantitative PCR (RT-qPCR) was used to analyze the expression of CASC2 and miR-183 in HCC tissues and cells. The viability of HCC SMMC-7721 and Huh-7 cells was detected through MTT assay. Colony formation assay was performed to assess the colony formation ability of HCC cells. The migration and invasion abilities of HCC cells were evaluated by Transwell assay. Western blot was conducted to examine levels of key Wnt/β-catenin signaling pathway factors, C-myc, cyclinD, survivin, and β-catenin. The interaction between CASC2 and miR-183 was affirmed by bioinformatics analysis and luciferase reporter assay. Results: CASC2 was down-regulated in HCC tissues and cell lines, while miR-183 was up-regulated. The expression of miR-183 was negatively correlated with CASC2 expression in HCC tissues. Overexpression of CASC2 inhibited cell viability, colony formation, migration, and invasion in HCC cells, as well as Wnt/β-catenin signaling pathway activity. miR-183 was a downstream target of CASC2 and negatively regulated by CASC2. Introduction of miR-183 rescued CASC2-induced suppressive effects on HCC cell viability, colony formation, migration, and invasion and Wnt/β-catenin signaling. Conclusion: CASC2 inhibited cell viability and the colony formation, migration, and invasion abilities of HCC cells by directly downregulating miR-183 through inactivation of the Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a serious diabetic complication caused by both environmental and genetic factors. Molecular mechanisms of DR may lead to the discovery of reliable prognostic indicators. The current study aimed to clarify the mechanism of microRNA-183 (miR-183) in DR in relation to the PI3K/Akt/VEGF signaling pathway. Microarray-based gene expression profiling of DR was used to identify the differentially expressed genes. Sprague-Dawley rats were used for the establishment of DR models, and then miR-183 was altered by mimic or inhibitor or BTG1 was downregulated by siRNA to explore the regulatory mechanism of miR-183 in DR. Furthermore, the expression of miR-183, CD34, endothelial nitric oxide synthase (eNOS), BTG1 and the PI3K/Akt/ VEGF signaling pathway-related genes as well as reactive oxygen species (ROS) level was determined, and the relationship between miR-183 and BTG1 was also verified. Cell growth, cell apoptosis, and angiogenesis were determined. Microarray analysis revealed the involvement of miR-183 in DR via the PI3K/Akt/VEGF signaling pathway by targeting BTG1. Upregulated miR-183 and downregulated BTG1 were observed in retinal tissues of DR rats. miR-183 overexpression activated the PI3K/Akt/VEGF signaling pathway, upregulated CD34, eNOS, and ROS, and inhibited BTG1. BTG1 was confirmed as a target gene of miR-183. miR-183 overexpression or BTG1 knockdown promoted cell growth and tube formation while it suppressed cell apoptosis of vascular endothelial cells in DR rats. In this study, we demonstrated that miR-183 silencing inhibiting cell growth and tube formation in vascular endothelial cells of DR rats via the PI3K/Akt/VEGF signaling pathway by upregulating BTG1. [ABSTRACT FROM AUTHOR]

Abstract Prostate cancer (PC) is the most common cancer in men; however, limited effect is obtained due to the therapy resistance. CASC2 acts as a tumor suppressor in human malignancies serving as a ceRNA for miRNAs; Sprouty2 (SPRY2), a key antagonist of RTK signaling, also serves as a tumor suppressor. Herein, CASC2 and SPRY2 expression was down-regulated in PC tissues and cell lines; the overexpression of CASC2 and SPRY2 could suppress PC cell proliferation, promote PC cell apoptosis, and enhance the sensitivity of PC cells to docetaxel. CASC2 positively regulated SPRY2 expression and inhibited downstream extracellular regulated protein kinases (ERK) signaling activation through SPRY2. By using online tools, miR-183 might be a direct target of CASC2, and might simultaneously bind to the 3′UTR of SPRY2. The direct binding between CASC2, miR-183 and SPRY2 was then validated; miR-183 inhibition enhanced the cytotoxicity of docetaxel on PC cells, which could be partially attenuated by SPRY2 knockdown. In summary, CASC2 competes with SPRY2 for miR-183 binding to rescue the expression of SPRY2 in PC cells, thus enhancing the sensitivity of PC cells to docetaxel through SPRY2 downstream ERK signaling pathway; CASC2 and SPRY2 might be novel adjuvants for docetaxel-based chemotherapy for PC. [ABSTRACT FROM AUTHOR]

Background: Neuropathic pain is a type of chronic pain that results from dysfunctions of the somatosensory nerve system. This study was aimed to investigate the effect of mTOR/VEGF signaling pathway on neuropathic pain and the regulation mechanisms of miR-183 on AMPA Receptors through mTOR/VEGF signaling pathway. Methods: Chronic compress injury (CCI) model was constructed in the current study, we used paw withdrawal mechanic threshold (PWMT) and paw withdrawal thermal latency (PWTL) to observe mTOR and VEGF receptors. Dual luciferase analysis, western blot and qRT-PCR were also applied to complete this experiment. Results: It was observed that the inhibition of mTOR and VEGF receptors could significantly relieve neuropathic pain in the CCI model. Moreover mTOR was confirmed as the direct target of miR-183. Furthermore, miR-183 could modulate VEGF through regulating mTOR expressions. We also found the expressions of AMPA receptors (i.e. GluR1 and GluR2), located in the downstream of mTOR/VEGF signaling pathway, were significantly upregulated when miR-183 was downregulated or when the mTOR/VEGF signaling pathway was activated. Conclusion: The inhibition of mTOR or VEGF receptors can significantly relieve neuropathic pain, and the upregulation of miR-183 can suppress AMPA receptors by inhibiting mTOR/VEGF pathway.

Dysregulation of miR-182 and miR-183 has been implicated in the progression of several human cancers. Our previous study showed that miR-182 and miR-183 are upregulated in malignant mesothelioma. However, their biological functions remain unclear. We performed in-situ hybridization to analyze the expression of miR-182 and miR-183 in human tissues. Functional analysis was performed by treatment of two mesothelioma cell lines (ACC-MESO1 and CRL-5915) with miR-182 and miR-183 inhibitors. RT-PCR and western blot analysis were conducted to analyze the expression of FOXO1, a known target of both miR-182 and miR-183. Mesothelioma cells treated with FOXO1 siRNA and miR-182/183 inhibitors were also analyzed by evaluating cell proliferation and invasion, as well as expression of FOXO1 and its downstream targets. We confirmed miR-182 expression in 25/29 cases and miR-183 expression in 29/29 cases of human mesothelioma tissue by in-situ hybridization. Notably, inhibition of miR-182 or miR-183 reduced cell proliferation, invasion, migration, and adhesion abilities of mesothelioma cells. Surprisingly, transfection with both miR-182 and miR-183 inhibitors showed even more effects on cell progression. Furthermore, FOXO1 was identified as a target of miR-182 and miR-183 in mesothelioma cells. Inhibition of miR-182 and miR-183 reduced cell proliferation ability via upregulation of FOXO1 and its downstream targets, namely, p27. Moreover, inhibition of miR-182 and miR-183 reduced the cell invasion properties of mesothelioma cells. Our findings indicated that miR-182 and miR-183 promote mesothelioma cell progression via downregulation of FOXO1 and p27. Targeting the miR-182/183—FOXO1 axis could serve as a novel treatment against malignant mesothelioma.

MicroRNAs (miRNAs) diagnostics can be useful for diagnosing or confirming miRNA abundance and are used in screening tests and to assess changes in miRNAs in vivo. At present, the use of traditional nucleic acid amplification assays to detect miRNAs has been limited in laboratory environment because of the time, equipment, and technical expertise required to perform these assays. A specialized, rapid affordable miRNA detection system is necessary when there are limited resources or point‐of‐care testing needs. We designed a portable and affordable fluorescence‐based miRNA detection system based on isothermal signal amplification technology, using SYBR Green II as a fluorescent dye. To reduce costs, we chose LED as a light source and designed the corresponding optical path for LED. The portable detection system shows results consistent with those by real‐time PCR, and can be used to detect miR‐183 with a limit of detection of approximately 2 fmol. We used the system to detect miR‐183 in tissues and blood from patients with hepatocellular carcinoma (HCC). The results from the portable detection device were compared with those from clinical trials and indicated that the miR‐183 fluorescence signal could successfully identify HCC and provide information related to cancer progression. [ABSTRACT FROM AUTHOR]

The expression levels of micro ribonucleic acid-183 (miR-183) and miR-141 in the lesion tissues of infected abdominal aortic aneurysm (IAAA) and their relationship with prognosis were investigated. Thirty-six patients with IAAA admitted and who underwent vascular surgery in People's Hospital of Shenzhen from June 2003 to June 2013 were selected. Reverse transcription polymerase chain reaction (RT-PCR) was utilized to detect the expression levels of miR-183 and miR-141 in lesion tissues and adjacent tissues 1 cm away from the aneurysm in 36 patients with IAAA. The relationship between the expression levels of miR-183 and miR-141 as well as the clinicopathological features of patients with IAAA were analyzed, and the factors influencing the prognosis of IAAA were analyzed by univariate and multiva-riate analysis. The expression levels of miR-183 and miR-141 were significantly downregulated in the lesions of patients with IAAA, and miR-183 and miR-141 levels in the lesion tissues of the IAAA patients were significantly lower than those in the adjacent tissues (P<0.05). The expression levels of miR-183 and miR-141 were not related to sex, age, history of hypertension, and alcoholism (P>0.05), but they were related to smoking history or aneurysm size (P<0.05). The overall survival rate of patients with IAAA was 41.6% (15/36). The multivariate analysis found that aneurysm size, low expression of miR-183, and low expression of miR-141 were independent factors affecting the prognosis of patients with IAAA. In conclusion, the expression levels of miR-183 and miR-141 in the lesion tissues of IAAA are low, and the lower the expression level is, the worse the prognosis gets. miR-183 and miR-141 can be used as predictors of prognosis in patients with IAAA. [ABSTRACT FROM AUTHOR]

Dysregulation of miR-182 and miR-183 has been implicated in the progression of several human cancers. Our previous study showed that miR-182 and miR-183 are upregulated in malignant mesothelioma. However, their biological functions remain unclear. We performed in-situ hybridization to analyze the expression of miR-182 and miR-183 in human tissues. Functional analysis was performed by treatment of two mesothelioma cell lines (ACC-MESO1 and CRL-5915) with miR-182 and miR-183 inhibitors. RT-PCR and western blot analysis were conducted to analyze the expression of FOXO1, a known target of both miR-182 and miR-183. Mesothelioma cells treated with FOXO1 siRNA and miR-182/183 inhibitors were also analyzed by evaluating cell proliferation and invasion, as well as expression of FOXO1 and its downstream targets. We confirmed miR-182 expression in 25/29 cases and miR-183 expression in 29/29 cases of human mesothelioma tissue by in-situ hybridization. Notably, inhibition of miR-182 or miR-183 reduced cell proliferation, invasion, migration, and adhesion abilities of mesothelioma cells. Surprisingly, transfection with both miR-182 and miR-183 inhibitors showed even more effects on cell progression. Furthermore, FOXO1 was identified as a target of miR-182 and miR-183 in mesothelioma cells. Inhibition of miR-182 and miR-183 reduced cell proliferation ability via upregulation of FOXO1 and its downstream targets, namely, p27. Moreover, inhibition of miR-182 and miR-183 reduced the cell invasion properties of mesothelioma cells. Our findings indicated that miR-182 and miR-183 promote mesothelioma cell progression via downregulation of FOXO1 and p27. Targeting the miR-182/183—FOXO1 axis could serve as a novel treatment against malignant mesothelioma. [ABSTRACT FROM AUTHOR]

As a well-conserved microRNA, miR-183 is ubiquitously expressed in many tissues and cells including backfat and the 3T3-L1 adipocytes; however, the mechanisms regulating miR-183 in adipogenesis remain poorly understood. Here, we explored the expression pattern and role of miR-183 in adipogenesis using hircine preadipocytes. The results showed that miR-183 was up-regulated during preadipocyte differentiation, and overexpression of miR-183 enhanced lipid accumulation and dramatically increased the mRNA expression of the adipogenic genes PPARγ , C/EBPα , SREBP-1c , FAS , and ACC . Using bioinformatics tools, we predicted Smad4 to be a target of miR-183. This was subsequently validated with a luciferase reporter assay. Overexpression of miR-183 suppressed the mRNA and protein levels of Smad4 significantly, whereas inhibiting miR-183 had the opposite effect. However, inhibition of Smad4 greatly accelerated lipid deposition and increased the expression of adipogenic genes which consists with the results of miR-183 overexpression. In conclusion, these results indicate that miR-183 promotes hircine preadipocyte differentiation by targeting Smad4 . [ABSTRACT FROM AUTHOR]

Background: Non-small-cell lung cancer (NSCLC) has one of the highest mortality rates among cancers worldwide, with a poor prognosis. Previous studies have reported that melittin, an active component of apitoxin, exerts anti-inflammatory and antitumor effects via vascular endothelial growth factor or FoxO1. Methods: CCK8, flow cytometry assay and Western blotting were performed to evaluate the effect of melittin on NSCLC. Results: The present study demonstrates that melittin activated caspase-2 by inhibiting miR-183 expression and, thus, induced NSCLC apoptosis in both NCI-H441 cancer cell line assays and an in vivo xenograft model. The results of the cell-based assays showed that melittin (2 µg/mL) robustly suppressed miR-183 expression level and resulted in decreased invasion and migration abilities of NCI-H441 cells. Additionally, a flow cytometry assay and Western blotting showed that melittin induced NSCLC NCI-H441 cell apoptosis along with significant elevation of caspase-2 and Bax, which are regulators of cell apoptosis, and reduced Bcl-2 protein expression compared with dimethyl sulfoxide control. Furthermore, subcutaneous injection of melittin (5 mg/kg) significantly suppressed NSCLC tumor growth compared with vehicle group tumors, determined through tumor size and weight. Conclusion: Taken together, the aforementioned findings contribute to identification of a novel therapeutic target in the treatment of NSCLC, in patients diagnosed with a high expression of miR-183. Moreover, this article provides solid evidence for the inhibitory effect of melittin on NSCLC cancer cell growth. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Previous investigations have shown that miR-183 is upregulated in bladder cancer (BC); however, its biological significance is not fully investigated. The goal of the current study is to analyze the function of miR-183 in BC development and progression. PATIENTS AND METHODS: 23 pairs of BC tumor and adjacent tissues were analyzed for miR-183 and c-Myc expression using Real-time polymerase chain reaction (PCR). MiR-183 expression was modulated by transfection of miR-183 or miR-183 inhibitor (miR-183-in). Protein expression of AXIN2, c-Myc and Cyclin D1 was determined by western blot. Cell growth activity and apoptotic potential were evaluated by cell viability assay and flow cytometry assay, respectively. Luciferase activity assay was conducted to determine whether AXIN2 is a direct target of miR-183. RESULTS: The expression of miR-183 is upregulated in BC tissues and cell lines, and is positively correlated with the expression of the Wnt target gene, c-Myc. MiR-183 positively regulated Wnt signaling activity by directly suppressing its negative feedback regulator, AXIN2. Overexpression of miR-183 promoted cell growth and inhibited apoptosis. Inhibition of miR-183 attenuated cell growth and enhanced apoptosis. The effect of miR-183 on cell growth and apoptosis can be abolished by knockdown of AXIN2. CONCLUSIONS: MiR-183 functions as an oncomiR in BC and upregulates Wnt signaling activity by directly suppressing AXIN2 expression. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS), a common and primary malignant bone tumor, is characterized by highly aggressive potency. Baicalein, a bioactive flavone isolated from Scutellaria baicalensis Georgi, has been shown to inhibit the progression of numerous tumors, including OS. However, the mechanisms by which baicalein protects against OS are still largely unknown. The results of the present study showed that administration of baicalein significantly inhibited the proliferation, migration and invasion and promoted apoptosis in MG-63 and Saos-2 cells. Ezrin was identified as a target gene of microRNA (miR)-183. MG-63 and Saos-2 cells treated with baicalein exhibited increased miR-183 levels and decreased Ezrin expression. Importantly, miR-183 inhibition and Ezrin overexpression abolished the effects of baicalein on MG-63 and Saos-2 cell proliferation, migration, invasion and apoptosis. Taken together, these findings suggest that baicalein inhibits the proliferation, migration and invasion and induces apoptosis in OS cells by activating the miR-183/Ezrin pathway, revealing a novel mechanism underlying anti-OS effects of baicalein. [ABSTRACT FROM AUTHOR]

The nutritional value of goat milk largely depends on its fatty acid content and composition. MicroRNAs (miRNAs) are a class of RNA molecules 18–25 nt in length that regulate gene expression and play crucial roles in several biological processes, including fatty acid metabolism. In this study, we analyzed the correlation between differentially expressed miRNAs in goat mammary tissue and the fatty acid composition of goat milk by using Pearson correlations. Results revealed that levels of miR-183 were highly and positively correlated with the fatty acid content in the milk. In addition, we demonstrated that overexpression of miR-183 inhibits milk fat metabolism and inhibition of miR-183 promotes milk fat metabolism. Using Western blot, we demonstrate that MST1 , one of the major elements of the Hippo signaling pathway, is a target of miR-183. Immunofluorescence assays revealed that miR-183 targets MST1 in the cytoplasm. In summary, data indicate that miR-183 inhibits the metabolism of milk fat by targeting the MST1 gene in the cytoplasm in goat mammary epithelial cells. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that microRNA-183 (miR-183) deregulates and plays major roles in many tumors. However, the role of miR-183 in osteosarcoma (OS) pathogenesis is still largely unknown. In this study, we first over-expressed and knocked down miR-183 in MG63 and U20S cells, respectively. Functional analyses showed that ectopic expression of miR-183 suppressed MG63 cell growth, migration, and invasion in vitro and in vivo, whereas knockdown of endogenous miR-183 in U20S cells significantly enhanced these abilities. Next, we characterized low density lipoprotein receptor-related protein 6 (LRP6) as a direct target of miR-183 that interacted with the 3′-untranslated region of LRP6. Furthermore, ectopic expression of LRP6 significantly abrogated the tumor-suppressive effect induced by miR-183. Finally, miR-183 regulated the tumor-suppressive functions in MG63 cells by suppressing the LRP6-Wnt/β-catenin signaling pathway. Therefore, our study demonstrates that miR-183 is a tumor suppressor microRNA that plays a major role in OS. [ABSTRACT FROM AUTHOR]

Background Glioma is the most common cause of cancer-related death. Therapy based on radiation seemed to effectively, while the radioresistance of several glioblastoma cells abolished the therapy. Thus, to employ the potential mechanism underlying the radioresistance is essential for glioma treatment. Methods Radioresistant cells were constructed using the X-ray radiation. Cell viability and apoptosis were detect using CCK-8 and Annexin-V/propidium iodide (PI), respectively. Real-time PCR and western blot were performed to determine gene expression. Luciferase reporter assay was carried out to detect the relationship between miR-183 and LRIG1. Mice xenotransplant model of glioma was established to detect the role of miR-183 in vivo. Results The expression of miR-183 was increased, while LRIG1 was decreased in resistant tissues rather than in sensitive tissues. The expression of LRIG1 was lower in radioresistant gliblastoma cell line U251R rather than in normal glioblastoma cell line U251. Overexpressed miR-183 suppressed cell apoptosis in radioresistance U251R cells (U251R). MiR-183 targets LRIG1 to regulate its expression. U251R cells transfected miR-183 inhibitor promoted the expression of LRIG1, and decreased the expression of EFGR and p-Akt, while U251R cells co-transfected with shRNA-LRIG1 abolished the effects of miR-183 knockdown. U251 cells transfected with miR-183 mimic decreased the expression of LRIG1, and promoted the expression of EFGR and p-Akt, while cells co-transfected with pcDNA-LRIG1 abolished the effects of miR-183 overexpression. In vivo experiments demonstrated that miR-183 inhibitor suppressed tumor growth, while miR-183 mimic promoted tumor growth. Conclusion MiR-183 overexpression promoted radioresistance of glioblastoma via down-regulating LRIG1 and increasing the activity of EFGR/Akt. [ABSTRACT FROM AUTHOR]

Objectives: Micro RNAs (miRNAs) have a major role in human cancerogenesis.The current study investigated the prognostic significance of miR-183 and miR-21 expression in tongue carcinoma patients. Material and method: For qPCR of miR-183 and miR-21 expression, total RNA isolated from 60 fresh-frozen tissue of tongue carcinomas was converted into cDNA by TaqMan MicroRNA Reverse Transcription Kit and quantified by TaqMan MicroRNAs Expression Assays. Fold changes in the miRNAs expression, normalized to RNU6B, were determined using 2 method, and dichotomized into high and low according to cut-off values derived from ROC curve analysis. Results: miR-183 emerged as promising discriminatory biomarker of poor outcome. Tissue over-expression of miR-183, observed in 68.3% of tongue carcinomas, was associated with clinical stage ( p = 0.037), tumor size ( p = 0.036), and high alcohol intake ( p = 0.034).The patients with miR-183 over-expression had significantly shorter overall survival ( p = 0.006) and a 5.666 times higher risk of poor outcome ( p = 0.005), while miR-21 over-expression carried a tendency towards poorer survival ( p = 0.073). However, multivariate analysis revealed that the recurrences were independent adverse prognostic factors, while miR-183 over-expression lost its significance. Conclusion: Our results suggests that over-expression of miR-183 in tumor tissue could be a potential marker of clinical stage and a poor survival of tongue carcinoma patients and may be associated with high alcohol consumption. Clinical relevance: Oncogenic miRNAs, such as the investigated miR-183 and miR-21, could be novel prognostic biomarkers of tumor progression and adverse clinical outcome in oral cancer, as well as novel therapeutic targets in cancer. [ABSTRACT FROM AUTHOR]