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Colorectal carcinoma (CRC) is one of the most common malignant tumors in the digestive tract. It was found that butyric acid could inhibit the expression of miR-183 to slow down malignant progression of CRC in the early stage. However, its regulatory mechanism remains unclear. This study screened the IC50 value of butyrate on inhibition of CRC cells malignant progression. Its inhibitory effects were detected by MTT assay, colony formation experiment, Transwell migration experiment, and apoptosis evaluation by flow cytometry. Next, the expressions of miR-183 and DNAJB4 were, respectively, determined in butyrate treated and miR-183 analog or si-DNAJB4-transfected CRC cells to further detect the role of upregulated miR-183 or silencing DNAJB4 in CRC cells malignant progression. Subsequently, the targeted regulatory relationship between miR-183 and si-DNAJB4 was confirmed by bioinformatic prediction tools and double luciferase report genes analysis method. The regulatory mechanism of butyrate on miR-183/DNAJB4 axis signal pathway was evaluated in molecular level, and verified in nude mouse xerograft tumor model and immunohistochemical analysis tests of Ki67 positive rates. The results displayed that butyrate with increased concentration can hinder the proliferation and improve apoptosis of CRC cells by decreasing the expression of miR-183. Thus, butyrate reduces miR-183 expression and increases DNAJB4 expression via the miR-183/DNAJB4 axis, ultimately inhibiting the malignant progression and increasing apoptosis of CRC. While over expression of miR-183 downregulate the expression of DNAJB4, which can reverse the inhibitory effect of butyrate. [ABSTRACT FROM AUTHOR]

As a common hypertensive complication of pregnancy, preeclampsia (PE) remains one of the leading causes of maternal and fetal with high morbidity and mortality worldwide. Much research has identified the vital functions of insulin‐like growth factor 1 (IGF‐1) in PE treatment. However, the combined roles and molecular mechanism of IGF‐1 and microRNAs (miRNAs) underlying PE remain unclear. Therefore, we first measured the expression of IGF‐1, zinc finger E‐box binding homeobox 1 (ZEB1) and microRNA‐183 (miR‐183) expression in the placenta tissues of patients with PE by Western blot analysis and RT‐qPCR. Interactions among IGF‐1, ZEB1 and miR‐183 were assessed by Western blot analysis, ChIP‐PCR and dual‐luciferase reporter gene assay. The effect of IGF‐1 on the biological characteristics of trophoblast cells was investigated by CCK‐8, colony formation assay and in vitro angiogenesis experiments after cells were transfected with si‐IGF‐1. Finally, a mouse eclampsia model induced by knockdown of IGF‐1 was established to confirm the in vitro effect of IGF‐1 on PE. We found that IGF‐1, ZEB1 and miR‐183 were highly expressed in the placental tissues of patients with PE. The knockdown of IGF‐1 resulted in reduced proliferation and invasion of trophoblast cells and was accompanied by inhibited angiogenesis. ZEB1 was positively regulated by IGF‐1 via ERK/MAPK pathway, which in turn inhibited miR‐153 expression by binding to the miR‐183 promoter. The in vitro experiments further confirmed that IGF‐1 knockdown could induce PE. To sum up, IGF‐1 knockdown elevated expression of miR‐183 by downregulating ZEB1, thereby promoting deterioration of PE. [ABSTRACT FROM AUTHOR]

Background: Liver regeneration is a highly orchestrated process concerning the modulation of various microRNAs (miRs). miR-183 was recently found to be involved in the process of liver regeneration, that miR-183 was remarkably up-regulated at 2–6 h after partial hepatectomy. Objective: This study was aimed to explore the mechanism of miR-183 in on liver regeneration. Methods: After partial hepatectomy (PH) or transfection, we measured the changes of miR-183 and programmed cell death protein 6 (PDCD6) levels in rats and the hepatocytes. The histopathology was observed with hematoxylin–eosin staining. The miR-183 mimic and inhibitor plasmids were intravenously injected into rats, and the liver weight/body weight ratio was calculated. The prediction of TargetScan and the validation of luciferase activity assay were employed to confirm the targeting relationship between miR-183 and PDCD6. The viability, apoptosis and cell cycle of transfected rat hepatocyte BRL-3A were determined via MTT and flow cytometry assays. Results: MiR-183 expression showed a contrary tendency with that of PDCD6 during liver regeneration. Enhanced miR-183 in rats could notably increase liver/body weight ratio, while its inhibition did conversely. Overexpressed PDCD6, a target of miR-183, repressed the viability and cell cycle in hepatocytes, whereas its silence led to contrary results. Overexpressed miR-183 in BRL-3A cells enhanced cell viability and promoted the cell cycle yet suppressed apoptosis, whereas its inhibition showed contrary results, which were offset by PDCD6. Conclusions: Collectively, miR-183 promoted liver regeneration via targeting PDCD6. [ABSTRACT FROM AUTHOR]

Aims: MicroRNA-183 (miR-183) is known to play important roles in osteoarthritis (OA) pain. The aims of this study were to explore the specific functions of miR-183 in OA pain and to investigate the underlying mechanisms. Methods: Clinical samples were collected from patients with OA, and a mouse model of OA pain was constructed by surgically induced destabilization of the medial meniscus (DMM). Reverse transcription quantitative polymerase chain reaction was employed to measure the expression of miR-183, transforming growth factor α (TGFα), C-C motif chemokine ligand 2 (CCL2), proinflammatory cytokines (interleukin (IL)-6, IL-1β, and tumour necrosis factor-α (TNF-α)), and pain-related factors (transient receptor potential vanilloid subtype-1 (TRPV1), voltage-gated sodium 1.3, 1.7, and 1.8 (Nav1.3, Nav1.7, and Nav1.8)). Expression of miR-183 in the dorsal root ganglia (DRG) of mice was evaluated by in situ hybridization. TGFα, CCL2, and C-C chemokine receptor type 2 (CCR2) levels were examined by immunoblot analysis and interaction between miR-183 and TGFα, determined by luciferase reporter assay. The extent of pain in mice was measured using a behavioural assay, and OA severity assessed by Safranin O and Fast Green staining. Immunofluorescent staining was conducted to examine the infiltration of macrophages in mouse DRG. Results: miR-183 was downregulated in tissue samples from patients and mice with OA. In DMM mice, overexpression of miR-183 inhibited the expression of proinflammatory cytokines (IL-6, IL-1β, TNF-α) and pain-related factors (TRPV1, Nav1.3, Nav1.7, Nav1.8) in DRG. OA pain was relieved by miR-183-mediated inhibition of macrophage infiltration, and dual luciferase reporter assay demonstrated that miR-183 directly targeted TGFα. Conclusion: Our data demonstrate that miR-183 can ameliorate OA pain by inhibiting the TGFα-CCL2/CCR2 signalling axis, providing an excellent therapeutic target for OA treatment.

Objective To explore the mechanism of miR-183 regulating mitochondrial autophagy in hypoxia/reoxygenated(H/R) hippocampal neurons. Methods The mouse hippocampal neuron HT-22 cells were collected and divided into control group, hypoxia/reoxygenation(H/R) model group (HR group), miR-183 over-expression group (miR-183 mimics group), and negative control group (miR-183 NC group). The anoxia and reoxygenation models were established by the method of anoxia 3 h+reoxygenation for 12 h, miR-183 mimics group and miR-183 NC group were transfected with miR-183 mimics and miR-183 NC on the basis of HR group. The survival rate of HT-22 cells was measured by MTT method, the ultra structure of mitochondria was microscopied and the levels of miR-183 and mitochondrial autophagy related genes Bnip3l mRNA were detected by RT-qPCR; Western blot was used to detect the expression of autophagy related proteins Bnip3l, beclin-1, ubiquitin and LC3 binding protein p62 (p62), microtubule related protein light chain 3 (LC3-Ⅱ)/LC3-Ⅰ. The targeting relationship between miR-183 and Bnip3l was verified by double Luciferase Report. Results Compared with control group, the autophagy of membrane structure in HT-22 cells increased in HR group and miR-183nc group, and melanin remained after autophagy, cell survival rate, miR-183 and p62 protein expression were all decreased (P＜0.05), the expression of Bnip3l mRNA and protein, beclin-1 and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)/LC3-Ⅰ proteins all increased(P＜0.05); In the miR-183 mimics group, except for the reduced cell survival rate, all the above indicators were opposite to the HR group with statistical significance (P＜0.05). Compared with miR-183 NC+ Bnip3l-3′UTR-WT group, the activity of luciferase in miR-183 mimics + Bnip3l-3′UTR-WT group decreased(P＜0.05). Conclusions The over-expression of miR-183 can target at inhibiting the expression of Bnip3l mRNA, the mitochondrial autophagy of HT-22 cells, and thus aggravate the damage of HT-22 cells caused by H/R.

Abstract Background Emerging evidence continues to highlight the significant role of microRNAs (miRNAs) in the regulation of cancer growth and metastasis. Herein, the current study aimed to elucidate the role of exosomal miR-183 in prostate cancer development. Methods Initially, public microarray-based gene expression profiling of prostate cancer was employed to identify differentially expressed miRNAs. The putative target gene TPM1 of miR-183 was subsequently predicted, followed by the application of a luciferase reporter assay and examination of the expression patterns in prostate cancer patients and cell lines. The effects of miR-183 and TPM1 on processes such as cell proliferation, invasion and migration were evaluated using in vitro gain- and loss-of-function experiments. The effect of PC3 cells-derived exosomal miR-183 was validated in LNCaP cells. In vivo experiments were also performed to examine the effect of miR-183 on prostate tumor growth. Results High expression of miR-183 accompanied with low expression of TPM1 was detected in prostate cancer. Our data indicated that miR-183 could target and downregulate TPM1, with the overexpression of miR-183 and exosomal miR-183 found to promote cell proliferation, migration, and invasion in prostate cancer. Furthermore, the tumor-promoting effect of exosome-mediated delivery of miR-183 was subsequently confirmed in a tumor xenograft model. Conclusions Taken together, the key findings of our study demonstrate that prostate cancer cell-derived exosomal miR-183 enhance prostate cancer cell proliferation, invasion and migration via the downregulation of TPM1, highlighting a promising therapeutic target against prostate cancer.

Abstract Background Neuropathic pain is related to the sustained activation of neuroglial cells and the production of proinflammatory cytokines in the spinal dorsal horn. However, the clinical efficacy of currently available treatments is very limited. The transcription factor nuclear factor κB (NF-κB) is a ubiquitously expressed protein family and considered to be crucial in autoimmunity. Thus, our study aimed to examine the influence of NF-κB p65 in chronic constriction injury (CCI)-induced neuropathic pain as well as its underlying mechanism. Methods A rat model of neuropathic pain was established by CCI induction followed by isolation of microglial cells. The binding of NF-κB p65 to HDAC2, of miR-183 to TXNIP, and of TXNIP to NLRP3 was investigated. Expression of miR-183, NF-κB p65, HDAC2, TXNIP, and NLRP3 was determined with their functions in CCI rats and microglial cells analyzed by gain- and loss-of-function experiments. Results NF-κB p65 and HDAC2 were upregulated while miR-183 was downregulated in the dorsal horn of the CCI rat spinal cord. NF-κB p65 was bound to the HDAC2 promoter and then increased its expression. HDAC2 reduced miR-183 expression by deacetylation of histone H4. Additionally, miR-183 negatively regulated TXNIP. Mechanistically, NF-κB p65 downregulated the miR-183 expression via the upregulation of HDAC2 and further induced inflammatory response by activating the TXNIP-NLRP3 inflammasome axis, thus aggravating the neuropathic pain in CCI rats and microglial cells. Conclusion These results revealed a novel transcriptional mechanism of interplay between NF-κB and HDAC2 focusing on neuropathic pain via the miR-183/TXNIP/NLRP3 axis.

Our study aims to investigate the effect of microRNA-183 (miR-183) on human umbilical vascular endothelial cells (HUVECs) injury by targeting IRS1. HUVECs injury was induced by oxidized low-density lipoprotein (ox-LDL). HUVECs were grouped so as to explore the role of ox-LDL and miR-183 in HUVECs injury, with the expression of miR-183 and IRS1 detected. Additionally, the related factors of oxidative stress and inflammation, as well as angiogenesis ability, proliferation, cell cycle, apoptosis, invasion, and migration abilities were also measured. Ox-LDL treatment could decrease the activity of HUVECs, increase the level of oxidative stress and inflammation, and induce the HUVECs injury. miR-183 could inhibit the expression of IRS1. The inhibition of miR-183 expression in ox-LDL-induced HUVECs injury could enhance cell activity, inhibit inflammatory level, and thus resist cell injury. Low expression of IRS1 could reverse the inhibition of miR-183 on HUVECs injury. This study highlights that inhibition of miR-183 expression may resist HUVECs injury by upregulating expression of IRS1.

Background/Aims: Disseminated tumors, known as metastases, are responsible for ninety-percent of mortality due to cancer. Epithelial to mesenchymal transition, a phenomenon required for morphological conversion of non-motile discoid shaped epithelial cells to highly motile spindle-shaped mesenchymal cells, is thought to be a pre-requisite for metastatic progression. Metastasis-associated 1 (MTA1) protein is a prime inducer of EMT and metastatic progression in all solid tumors including hepatocellular carcinoma (HCC). However, the molecular mechanisms that regulate the expression and function of MTA1 in HCC have not been elucidated. Methods: In silico prediction algorithms were used to find microRNAs (miRNAs) that may target MTA1. We examined the relationship between the expression of MTA1 and miR-183 using quantitative real time PCR. We also determined the levels of the MTA1 protein using immunohistochemistry. Reporter assays, in the presence and absence of the miR-183 mimic, were used to confirm MTA1 as a bona fide target of miR183. The effect of miR-183 on HCC pathogenesis was determined using a combination of in vitro migration and invasion assay, together with in vivo xenograft experiments. The correlation between miR-183 and MTA1 expression was also studied in samples from HCC patients, and in The Cancer Genome Atlas dataset. Results: Analysis of the sequence database revealed that MTA1 is a putative target of miR-183. MTA1 protein and RNA expression showed opposite trends to miR-183 expression in breast, renal, prostate, and testicular tissue samples from cancer patients, and in the metastatic HCC cell line HepG2. An inverse correlation was also observed between MTA1 (high) and miR-183 (low) expression within samples from HHC patients and in the TCGA dataset. Reporter assays in HepG2 cells showed that miR-183 could inhibit translation of a reporter harboring the wild-type, but not the mutant miR-183 3’-untranslated region (UTR). In addition, miR-183 significantly inhibited in vitro migration and invasion in HepG2 cells, and in vivo hepatic metastasis. Conclusion: Our results reveal a novel post-transcriptional regulatory mechanism for MTA1 expression via miR-183, which is suppressed during HCC pathogenesis.

Background: Emerging evidence continues to highlight the significant role of microRNAs (miRNAs) in the regulation of cancer growth and metastasis. Herein, the current study aimed to elucidate the role of exosomal miR-183 in prostate cancer development. Methods: Initially, public microarray-based gene expression profiling of prostate cancer was employed to identify differentially expressed miRNAs. The putative target gene TPM1 of miR-183 was subsequently predicted, followed by the application of a luciferase reporter assay and examination of the expression patterns in prostate cancer patients and cell lines. The effects of miR-183 and TPM1 on processes such as cell proliferation, invasion and migration were evaluated using in vitro gain- and loss-of-function experiments. The effect of PC3 cells-derived exosomal miR-183 was validated in LNCaP cells. In vivo experiments were also performed to examine the effect of miR-183 on prostate tumor growth. Results: High expression of miR-183 accompanied with low expression of TPM1 was detected in prostate cancer. Our data indicated that miR-183 could target and downregulate TPM1, with the overexpression of miR-183 and exosomal miR-183 found to promote cell proliferation, migration, and invasion in prostate cancer. Furthermore, the tumor-promoting effect of exosome-mediated delivery of miR-183 was subsequently confirmed in a tumor xenograft model. Conclusions: Taken together, the key findings of our study demonstrate that prostate cancer cell-derived exosomal miR-183 enhance prostate cancer cell proliferation, invasion and migration via the downregulation of TPM1, highlighting a promising therapeutic target against prostate cancer. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a hypertensive disorder of uncertain etiology that is the leading cause of maternal and fetal morbidity or mortality. The dysregulation of microRNAs (miRNAs) has been highlighted as a potential factor involved in the development of PE. Therefore, our study investigated a novel miRNA, miRNA 183 (miR- 183), and its underlying association with PE. Expression of miR-183, forkhead box P1 (FOXP1), and G protein subunit gamma 7 (GNG7) in placental tissues of patients with PE was determined. Gain- and loss-of-function experiments were conducted to explore modulatory effects of miR-183, FOXP1, and GNG7 on the viability, invasion, and angiogenesis of trophoblast cells in PE. Finally, we undertook in vivo studies to explore effects of FOXP1 in the PE model. The results revealed suppressed expression of FOXP1 and significant elevations in miR-183 and GNG7 expression in placental tissues of PE patients. FOXP1 was observed to promote proliferation, invasion, and angiogenesis in human chorionic trophoblastic cells. miR-183 resulted in depletion of FOXP1 expression, while FOXP1 was capable of restraining GNG7 expression and promoting the mTOR pathway. The findings confirmed the effects of FOXP1 on PE. In conclusion, miR-183 exhibits an inhibitory role in PE through suppression of FOXP1 and upregulation of GNG7. [ABSTRACT FROM AUTHOR]

Backgrounds/Aims: MicroRNAs (miRs) often contribute to the progression of non-small cell lung cancer (NSCLC) via regulation of mRNAs that are involved in lung homeostasis. We conducted a study aimed at exploring the roles of miR-183 in the proliferation, epithelial-mesenchymal transition (EMT), invasion and migration of human NSCLC cells via targeting MTA1. Methods: NSCLC and adjacent normal tissues were collected from 194 patients with NSCLC. Positive expression of MTA1 protein was detected by immunohistochemistry. The highest levels of expression of miR-183 were detected using RT-qPCR in SPC-A-1 cells, which were selected and assigned to the following groups: blank, negative control (NC), miR-183 mimic, miR-183 inhibitor, siRNA-MTA1, and miR-183 inhibitor + siRNA-MTA1. The expression of miR-183 and the mRNA and protein expression of MTA1, E-cadherin, Vimentin, Snail, PCNA, Bax and Bcl-2 in tissues and transfected cells were measured using RT-qPCR and western blot analysis. Cell proliferation, apoptosis, migration and invasion were evaluated by CCK-8, flow cytometry, scratch tests and Transwell assays. Tumor xenografts were conducted in nude mice to determine tumor growth. Results: SPC-A-1 cells with the highest levels of miR-183 expression were selected. Compared with adjacent normal tissues, the expression of miR-183 and the mRNA and protein expression of E-cadherin and Bax were decreased in NSCLC tissues, while mRNA and protein expression of MTA1, Vimentin, snail, PCNA and Bcl-2 were increased. MiR-183 was over-expressed in the miR-183 mimic group and under-expressed in the miR-183 inhibitor and miR-183 inhibitor + siRNA-MTA1 groups. In the miR-183 mimic and siRNA-MTA1 groups, the mRNA and protein expression of E-cadherin and Bax, as well as cell apoptosis, were enhanced, while the expression levels of MTA1, Vimentin, snail, PCNA and Bcl-2 mRNA and protein, cell proliferation, migration, invasion and tumor growth were reduced relative to the blank and NC groups. The miR-183 inhibitor group exhibited an opposite trend. Conclusion: Our study indicates that miR-183 down-regulates MTA1 to inhibit the proliferation, EMT, migration and invasion of human NSCLC cells.

Background: Neuropathic pain is related to the sustained activation of neuroglial cells and the production of proinflammatory cytokines in the spinal dorsal horn. However, the clinical efficacy of currently available treatments is very limited. The transcription factor nuclear factor κB (NF-κB) is a ubiquitously expressed protein family and considered to be crucial in autoimmunity. Thus, our study aimed to examine the influence of NF-κB p65 in chronic constriction injury (CCI)-induced neuropathic pain as well as its underlying mechanism.Methods: A rat model of neuropathic pain was established by CCI induction followed by isolation of microglial cells. The binding of NF-κB p65 to HDAC2, of miR-183 to TXNIP, and of TXNIP to NLRP3 was investigated. Expression of miR-183, NF-κB p65, HDAC2, TXNIP, and NLRP3 was determined with their functions in CCI rats and microglial cells analyzed by gain- and loss-of-function experiments.Results: NF-κB p65 and HDAC2 were upregulated while miR-183 was downregulated in the dorsal horn of the CCI rat spinal cord. NF-κB p65 was bound to the HDAC2 promoter and then increased its expression. HDAC2 reduced miR-183 expression by deacetylation of histone H4. Additionally, miR-183 negatively regulated TXNIP. Mechanistically, NF-κB p65 downregulated the miR-183 expression via the upregulation of HDAC2 and further induced inflammatory response by activating the TXNIP-NLRP3 inflammasome axis, thus aggravating the neuropathic pain in CCI rats and microglial cells.Conclusion: These results revealed a novel transcriptional mechanism of interplay between NF-κB and HDAC2 focusing on neuropathic pain via the miR-183/TXNIP/NLRP3 axis. [ABSTRACT FROM AUTHOR]

Our study aims to investigate the effect of microRNA-183 (miR-183) on human umbilical vascular endothelial cells (HUVECs) injury by targeting IRS1. HUVECs injury was induced by oxidized low-density lipoprotein (ox-LDL). HUVECs were grouped so as to explore the role of ox-LDL and miR-183 in HUVECs injury, with the expression of miR-183 and IRS1 detected. Additionally, the related factors of oxidative stress and inflammation, as well as angiogenesis ability, proliferation, cell cycle, apoptosis, invasion, and migration abilities were also measured. Ox-LDL treatment could decrease the activity of HUVECs, increase the level of oxidative stress and inflammation, and induce the HUVECs injury. miR-183 could inhibit the expression of IRS1. The inhibition of miR-183 expression in ox-LDL-induced HUVECs injury could enhance cell activity, inhibit inflammatory level, and thus resist cell injury. Low expression of IRS1 could reverse the inhibition of miR-183 on HUVECs injury. This study highlights that inhibition of miR-183 expression may resist HUVECs injury by upregulating expression of IRS1. [ABSTRACT FROM AUTHOR]

To evaluate the serum levels of microRNA-183 (miR-183) and thymidine kinase 1 (TK1) in colorectal cancer patients and their clinical value as biomarkers for colorectal cancer auxiliary diagnosis.

Recently, the impacts of microRNAs (miRNAs) have been identified in epilepsy (EP), this study was designed to assess the role of miR-183 in hippocampal neuron injury in EP. Rat EP models were established by injected with lithium-pilocarpine. The pathological observation of rats' hippocampus sections was conducted. Expression of miR-183, Foxp1, Jak1, Stat1, and Stat3 in rats' hippocampal tissues was determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. The proliferation ability and the apoptosis of the rats' neurons were measured. Furthermore, the target relation between miR-183 and Foxp1 was determined by bioinformatics analysis and dual-luciferase gene reporter assay. The levels of miR-183, Jak1, Stat1, and Stat3 were elevated, and the expression of Foxp1 was declined in EP rats' hippocampal tissues. Inhibited miR-183 could up-regulate Foxp1, inhibited miR-183 together with up-regulated Foxp1 could repress hippocampal neuron injury, promote neuron proliferation, suppress neuron apoptosis, and inactivate the Jak/Stat signaling pathway, resulting in an attenuation of EP progression. Moreover, down-regulated Foxp1 could reverse the attenuation of EP progression which was contributed by inhibited miR-183. Our study implies that inhibited miR-183 could up-regulate Foxp1, resulting in an inactivation of the Jak/Stat signaling pathway and promotion of neuron proliferation, as well as inhibition of apoptosis of hippocampal neurons in EP rats, by which the hippocampal neuron injury and EP progression could be repressed. [ABSTRACT FROM AUTHOR]

Ischemic stroke represents 87% of all strokes, and is the third leading cause of disability and mortality worldwide. The cause of ischemic stroke is the obstruction of blood flow through the artery that supplies oxygen-rich blood to the brain, with ischemia-reperfusion injury as its major cause. microRNAs (miRNA) are small non-coding RNAs, which serve important roles in the regulation of gene expression at the post-transcription level. The aim of the present study was to investigate the effect of miRNA-183 (miR-183) on microglia activation in rats with cerebral ischemia-reperfusion injury. To this end, a rat cerebral ischemia-reperfusion injury model was established. The results indicated that miR-183 expression was decreased by cerebral ischemia-reperfusion. In addition, treatment using miR-183 agomir significantly reduced the neurological function scores, percentage of cerebral infarction volume, and ionized calcium-binding adapter molecule-1 (IBA-1)-positive cells in the CA1 area of the hippocampus in rats subjected to cerebral ischemia-reperfusion injury, implicating a neuroprotective role for miR-183. MiR-183 agomir treatment also decreased the expression of pro-inflammatory-associated proteins interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α. Finally, the expression of the nuclear factor (NF)-κB p65 and IκBα was decreased and increased by miR-183 agomir treatment, respectively, indicating inhibition of the NF-κB signaling pathway. These observations suggest that miR-183 regulates the activation of microglia in rats with cerebral ischemia-reperfusion injury by inhibiting the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is primarily caused by ischemic heart or coronary artery disease and is a major cause of mortality worldwide. Thus, it is necessary to establish reliable biochemical markers for the early diagnosis of MI. MicroRNAs (miRNAs or miR) have been demonstrated to circulate in biological fluids and are enclosed in extracellular vesicles, including exosomes. The current study assessed the differential expression of exosomal miRNAs in the plasma of patients with MI and healthy individuals, and the possible mechanism involved. Plasma-derived exosomes were isolated from patients with MI and healthy control individuals, and vesicles with a membrane were observed using transmission electron microscopy. Furthermore, an exosomal miRNA expression profile was compared between patients with MI and healthy individuals using a miRNA microarray. Significantly differentially expressed miRNAs were validated using reverse transcription-quantitative polymerase chain reaction. To the best of our knowledge, the present study was the first to demonstrate that miR-183 was markedly upregulated in patients with MI compared with healthy individuals. In addition, the relative exosomal miR-183 level increased with the degree of myocardial ischemic injury. Additionally, GO and KEGG analyses demonstrated that miR-183 is primarily involved in cell communication, protein kinase activity regulation and adrenergic signaling in cardiomyocytes. Furthermore, a protein-protein interaction network of all the miR-183 target genes was constructed. The results demonstrated that five core genes (PPP2CB, PPP2CA, PRKCA, PPP2CA, PPP2R5C and PPP2R2A) in the PPI network were also associated with protein kinase activity regulation and adrenergic signaling in cardiomyocytes. Taken together, these data demonstrate that exosomal miR-183 derived from the serum of patients with MI may be a novel diagnostic biomarker involved in the regulation of protein kinase activity. miR-183 may therefore be further developed for clinical use to benefit patients with coronary artery diseases. [ABSTRACT FROM AUTHOR]

Sevoflurane has been commonly utilized in nonobstetric surgeries in pregnant women, and its impacts on fetal brain are still not completely known. Ectopic NR4A2 expression has been reported to be related with familial Parkinson disease, and through dual luciferase we found that NR4A2 is a target gene of microRNA‐183 (miR‐183). We proposed a hypothesis that miR‐183 may participate in the process by targeting NR4A2 in neurons after sevoflurane anesthesia. To verify the effect of sevoflurane on hippocampal neural stem cells (NSCs) proliferation and differentiation, we conducted EdU assay and immunofluorescence staining. Next, for better understanding of the impact of miR‐183, we altered the miR‐183 expression using mimic and inhibitor. Meanwhile, the targeting relationship between miR‐183 and NR4A2 was validated by a bioinformatics website and dual‐luciferase reporter gene assay. Finally, expressions of miR‐184, NR4A2, SRY (sex‐determining region Y)‐box 2 (Sox2), and brain‐derived neurotrophic factor (BDNF) were determined and evaluated by reverse transcription quantitative polymerase chain reaction and western blot analysis. First, sevoflurane was determined a crucial factor in biological behaviors of hippocampal NSCs. Moreover, upregulated miR‐183 expression by mimic inhibited the proliferation and differentiation of NSCs. Sevoflurane negatively regulated NR4A2 and Sox2 expressions but positively regulated miR‐183 and BDNF expressions. Our findings revealed the underlying novel mechanism by which sevoflurane inhibits hippocampal NSC proliferation and differentiation through interaction with miR‐183 and NR4A2. The study provides reliable reference for safe application of sevoflurane anesthesia in neonates. Our findings revealed the underlying novel mechanism by which sevoflurane inhibits hippocampal neural stem cell proliferation and differentiation through interaction with microRNA‐183 and NR4A2. The study provides reliable reference for safe application of sevoflurane anesthesia in neonates. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is a common malignancy with a poorly understood pathogenesis. Currently, the efficacy of anti-PC therapies is insufficient, partially due to the chemoresistance of cancer cells. The present study aimed to elucidate the role of miR-183 in the proliferation, apoptosis, and chemosensitivity to 5-fluorouracil and gemcitabine of human PC cells and the associated mechanisms. PANC-1 cells were transfected with microRNA (miR)-183 inhibitors, and the effect of miR-183 on cell proliferation was evaluated via MTT assay. Apoptosis and cell cycle distribution were determined by flow cytometry. In vivo tumor xenograft models of PANC-1 cells were generated in BALB/c nude mice to examine the effect of miR-183 downregulation on tumor growth. Furthermore, components of the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway were examined via reverse transcription-quantitative polymerase chain reaction and western blotting in the collected cells. Finally, PANC-1 cells were treated with 5-fluorouracil or gemcitabine and transfected with miR-183 inhibitors, and the viability of cells was determined by MTT assay. The results demonstrated that knockdown of miR-183 could significantly decrease proliferation and promote apoptosis of PANC-1 cells. The cells transfected with miR-183 inhibitors were significantly arrested at the G1 phase (P<0.01). Furthermore, miR-183 downregulation led to significant decreases in the mRNA levels of PI3K, Akt and B cell lymphoma-2 (Bcl-2) expression (P<0.001), and significant increases in PTEN and Bcl-2 associated X protein expression in PANC-1 cells (P<0.001). Knockdown of miR-183 was able to significantly increase the chemosensitivity of PANC-1 cells to 5-fluorouracil and gemcitabine. These results indicate that downregulation of miR-183 can inhibit the growth of PC cells in vitro and in vivo, and increase cell sensitivity to 5-fluorouracil and gemcitabine through regulating the PTEN/PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract MircoRNAs (miRs) are small molecules that regulate gene expression at the posttranscriptional level. They have been proposed to be involved in the regulation of several immune responses including autoimmunity. Here, we identified miR-183 and miR-96 to be highly expressed in CD4+ T cells from peripheral blood of Graves' orbitopathy (GO) patients as well as in human and murine T cells upon activation in vitro. By using Luciferase-based binding assays, we identified EGR-1 as target for miR-183 and miR-96. Overexpression of miR-183 and miR-96 in murine CD4+ T cells by retroviral gene transfer resulted in decreased EGR-1 and PTEN expression, elevated Akt phosphorylation and enhanced proliferation. In contrast, treatment of murine CD4+ T cells with specific antagomiRs increased EGR-1 and PTEN expression and interfered with the proliferative activity upon stimulation in vitro. Strikingly, adoptive transfer of miR-183 and miR-96 overexpressing antigen-specific T cells into INS-HA/Rag2KO mice accelerated the development of autoimmune diabetes, whereas transfer of antagomiR-treated cells delayed the disease onset. These results indicate that miR-183 and miR-96 have the ability to regulate the strength of T cell activation and thereby the development and severity of T cell-dependent autoimmune diseases. Highlights • Elevated miRNA-183/96 expression in CD4+ T cells from Graves' orbitopathy patients. • MiRNA-183/96 regulate T cell proliferation via the EGR-1/PTEN/Akt axis. • AntagomiR-183/96 treatment of T cells delays the onset of autoimmune diabetes. [ABSTRACT FROM AUTHOR]

This study investigated whether microRNA-183 and microRNA-141 in nasopharyngeal carcinoma (NPC) lesions are potential risk factors for poor prognosis. A total of 317 NPC patients admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2010 to March 2015 were included. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect the expression of microRNA-183 and microRNA-141 in lesions and adjacent tissues, and the relationship between the microRNA-183 and microRNA-141 expression levels and prognosis was analyzed. The expression levels of microRNA-183 and microRNA-141 in lesions were significantly higher than those in adjacent tissues (p<0.05). Patients with distant metastasis had significantly higher expression levels of microRNA-183 and microRNA-141 than patients without distant metastasis (p<0.01). Patients with disease-free survival (DFS) <3 years showed significantly higher expression levels of microRNA-183 and microRNA-141 than those with DFS ≥3 years (p<0.01). NPC patients with high expression levels of microRNA-183 and microRNA-141 showed poor prognosis. MicroRNA-183 and microRNA-141 may play an important role in the distant metastasis of NPC, and have a great impact on prognosis. [ABSTRACT FROM AUTHOR]

To assess the influence of microRNA-183 (miR-183) on the migration and invasion of A375 human melanoma cells, an A375 cell line with stable miR-183 overexpression or knockdown was constructed using lentiviral transfection. The change of miR-183 expression in these cells and in non-transfected controls was verified using reverse transcription-quantitative polymerase chain reaction. The impact of miR-183 on experimental A375 cell migration and invasion was assessed using a scratch and Transwell assay. The expression of Ezrin and matrix metalloprotease-9 (MMP-9), which are two mediator proteins that serve roles in tumor cell migration and invasion, were analyzed in each cell group via western blotting. The results of the present study indicated that miR-183 overexpression significantly inhibits A375 cell migration and invasion, which may be facilitated by miR-183 knockdown. Furthermore, Ezrin and MMP-9 protein levels were negatively associated with miR-183 expression, indicating that miR-183 may function as a tumor suppressor by inhibiting the expression of these two proteins. Additionally, miR-183 downregulation may be associated with the progression of melanoma. [ABSTRACT FROM AUTHOR]

Background/Aims: Disseminated tumors, known as metastases, are responsible for ninety-percent of mortality due to cancer. Epithelial to mesenchymal transition, a phenomenon required for morphological conversion of non-motile discoid shaped epithelial cells to highly motile spindle-shaped mesenchymal cells, is thought to be a pre-requisite for metastatic progression. Metastasis-associated 1 (MTA1) protein is a prime inducer of EMT and metastatic progression in all solid tumors including hepatocellular carcinoma (HCC). However, the molecular mechanisms that regulate the expression and function of MTA1 in HCC have not been elucidated. Methods:In silico prediction algorithms were used to find microRNAs (miRNAs) that may target MTA1. We examined the relationship between the expression of MTA1 and miR-183 using quantitative real time PCR. We also determined the levels of the MTA1 protein using immunohistochemistry. Reporter assays, in the presence and absence of the miR-183 mimic, were used to confirm MTA1 as a bona fide target of miR183. The effect of miR-183 on HCC pathogenesis was determined using a combination of in vitro migration and invasion assay, together with in vivo xenograft experiments. The correlation between miR-183 and MTA1 expression was also studied in samples from HCC patients, and in The Cancer Genome Atlas dataset. Results: Analysis of the sequence database revealed that MTA1 is a putative target of miR-183. MTA1 protein and RNA expression showed opposite trends to miR-183 expression in breast, renal, prostate, and testicular tissue samples from cancer patients, and in the metastatic HCC cell line HepG2. An inverse correlation was also observed between MTA1 (high) and miR-183 (low) expression within samples from HHC patients and in the TCGA dataset. Reporter assays in HepG2 cells showed that miR-183 could inhibit translation of a reporter harboring the wild-type, but not the mutant miR-183 3'-untranslated region (UTR). In addition, miR-183 significantly inhibited in vitro migration and invasion in HepG2 cells, and in vivo hepatic metastasis. Conclusion: Our results reveal a novel post-transcriptional regulatory mechanism for MTA1 expression via miR-183, which is suppressed during HCC pathogenesis. [ABSTRACT FROM AUTHOR]

Auditory hair cell regeneration following injury is critical to hearing restoration. The Notch signaling pathway participates in the regulation of inner ear development and cell differentiation. Recent evidence suggests that microRNA (miR)‑183 has a similar role in the inner ear. However, it is unclear how Notch signaling functions in hair cell regeneration in mammals and if there is cross‑talk between Notch signaling and miR‑183. The present study used a gentamicin‑induced cochlear injury mouse model. Gentamicin‑induced damage of the hair cells activated the Notch signaling pathway and downregulated miR‑183 expression. Notch signaling inhibition by the γ‑secretase inhibitor, 24‑diamino‑5‑phenylthiazole (DAPT), attenuated gentamicin‑induced hair cell loss and reversed the downregulation of miR‑183 expression. Further investigation revealed that the novel hair cells produced, induced by DAPT, were derived from transdifferentiated supporting cells. Additionally, myosin VI‑positive hair cell numbers were increased by Notch signaling inhibition in in vitro experiments with cultured neonatal mouse inner ear precursor cells. This effect was reversed by miR‑183 inhibition. These findings indicate that the Notch signaling pathway served a repressing role during the regeneration of hair cells. Inhibiting this signal improved hair cell regeneration in the gentamicin‑damaged cochlear model. miR‑183 was demonstrated to be involved in hair cell differentiation and regeneration, and was required for the differentiation of the Notch‑inhibited hair cells. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the effects of microRNA (miR)-183 on vitality, invasion, metastasis and apoptosis in osteosarcoma (OS) cells, mediated by its binding to metastasis-associated protein 1 (MTA1). A dual luciferase reporter assay was performed to determine whether MTA1 was a direct target of miR-183. Cell Counting Kit-8, Transwell, scratch-wound healing, fluorescence-activated cell sorting andterminal deoxynucleotidyl transferase dUTP nick end labeling assays were also performed to investigate the effects of miR-183 expression on the proliferation, invasion, migration and apoptosis of MG63 cells. It was demonstrated that that MTA1 expression levels were significantly higher in OS tissues and MG63 cells compared with corresponding adjacent noncancerous tissues and normal cells, respectively, while miR-183 expression levels were significantly lower (both P<0.05). Furthermore, miR-183 overexpression downregulated MTA1 levels and inhibited cell proliferation (P<0.05), migration (P<0.05) and invasion (P<0.01), as well as promoting apoptosis (P<0.01) by binding to the 3'-untranslated region of MTA1. These results indicate that miR-183 inhibits the vitality, invasion, migration and apoptosis of the OS cell line MG63 by targeting MTA1. These findings may contribute to the development of novel clinical therapeutic approaches for the treatment of OS. [ABSTRACT FROM AUTHOR]

Backgrounds/Aims: MicroRNAs (miRs) often contribute to the progression of non-small cell lung cancer (NSCLC) via regulation of mRNAs that are involved in lung homeostasis. We conducted a study aimed at exploring the roles of miR-183 in the proliferation, epithelial-mesenchymal transition (EMT), invasion and migration of human NSCLC cells via targeting MTA1. Methods: NSCLC and adjacent normal tissues were collected from 194 patients with NSCLC. Positive expression of MTA1 protein was detected by immunohistochemistry. The highest levels of expression of miR-183 were detected using RT-qPCR in SPC-A-1 cells, which were selected and assigned to the following groups: blank, negative control (NC), miR-183 mimic, miR-183 inhibitor, siRNA-MTA1, and miR-183 inhibitor + siRNA-MTA1. The expression of miR-183 and the mRNA and protein expression of MTA1, E-cadherin, Vimentin, Snail, PCNA, Bax and Bcl-2 in tissues and transfected cells were measured using RT-qPCR and western blot analysis. Cell proliferation, apoptosis, migration and invasion were evaluated by CCK-8, flow cytometry, scratch tests and Transwell assays. Tumor xenografts were conducted in nude mice to determine tumor growth. Results: SPC-A-1 cells with the highest levels of miR-183 expression were selected. Compared with adjacent normal tissues, the expression of miR-183 and the mRNA and protein expression of E-cadherin and Bax were decreased in NSCLC tissues, while mRNA and protein expression of MTA1, Vimentin, snail, PCNA and Bcl-2 were increased. MiR-183 was over-expressed in the miR-183 mimic group and under-expressed in the miR-183 inhibitor and miR-183 inhibitor + siRNA-MTA1 groups. In the miR-183 mimic and siRNA-MTA1 groups, the mRNA and protein expression of E-cadherin and Bax, as well as cell apoptosis, were enhanced, while the expression levels of MTA1, Vimentin, snail, PCNA and Bcl-2 mRNA and protein, cell proliferation, migration, invasion and tumor growth were reduced relative to the blank and NC groups. The miR-183 inhibitor group exhibited an opposite trend. Conclusion: Our study indicates that miR-183 down-regulates MTA1 to inhibit the proliferation, EMT, migration and invasion of human NSCLC cells. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is insensitive to conventional chemotherapy and radiotherapy, and its prognosis remains poor. Targeted therapy is a novel technique for the treatment of RCC. The present study aimed to determine the precise effects of microRNA-183 (miR-183) on RCC. Reverse transcription-quantitative polymerase chain reaction analysis was conducted in order to analyze the expression level of miR-183 in RCC cell lines. Cell transfection, viability assays and invasion assays were also performed, followed by western blot analysis and a luciferase reporter assay, in order to examine the effects of miR-183. The expression of miR-183 was upregulated in all four RCC cell lines compared with the immortalized normal proximal tubule epithelial HK-2 cell line. The cell viability and invasion assays demonstrated that decreased expression of miR-183 suppressed RCC cell proliferation and invasion in vitro. Furthermore, the present study identified that Dickkopf-related protein-3 (DKK-3) was a direct target of miR-183 in RCC. The results demonstrated that miR-183 functioned as an oncogene by downregulating DKK-3 expression and that it provided a potential diagnostic, prognostic and therapeutic target for RCC. [ABSTRACT FROM AUTHOR]

Objective This study aims to explore effects of miR-183 on epithelial-mesenchymal transition (EMT) and invasion by targeting MTA1 in human pancreatic cancer (PC) cells. Methods Totally, 108 PC patients admitted in Wenzhou Central Hospital and Wenzhou People's Hospital, The Dingli Clinical Institute of Wenzhou Medical University from March 2010 to March 2014 were enrolled. qRT-PCR and immunohistochemistry were applied to examine expression of MTA1 mRNA and protein. Samples were divided into 6 groups: blank, NC, miR-183 mimics, miR-183 inhibitors, MTA1 -siRNA and miR-183 inhibitors + MTA1 -siRNA groups. CCK8 method was employed for determining cell proliferation rate, flow cytometry for cell apoptosis rate, scratch test for cell migration and Transwell assay for cell invasion. qRT-PCR and Western blotting were used to determine expression of MTA1 , E-cadherin and Vimentin mRNA and protein. Results Positive expression rate of MTA1 was upregulated in PC tissues, and expression of miR-183 and MTA1 was associated with differentiation, migration, tumor size, TNM. The miR-183 mimics and MTA1 -siRNA groups showed a decrease in proliferation, migration and invasion, whereas increased apoptosis, in comparison with blank and NC groups, as expression of MTA1 and Vimentin mRNA and protein were reduced, expression of E-cadherin mRNA and protein was elevated. Compared to blank and NC groups, the miR-183 inhibitors group exhibited enhanced proliferation, migration and invasion and inhibited apoptosis; increased expressions of MTA1 and Vimentin mRNA and protein and decreased expressions of E-cadherin mRNA and protein. Conclusion Our study supported that miR-183 could repress EMT and invasion of human PC cells through inhibition of MTA1 expression. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate roles of microRNA (miR)-183 in pediatric acute myeloid leukemia (AML). Methods: miR-183 expression in bone marrow and patients' sera of childhood AML was detected by real-time quantitative PCR. Functions of miR-183 in malignant phenotypes of two leukemia cell lines were then evaluated. Additionally, putative targets of miR-183 were predicted using three miRNA target prediction algorithms and validated by luciferase reporter assay. Clinical relevance of miR-183 and its target gene were further determined. Results: miR-183 expression in bone marrow and patients' sera of childhood AML was both significantly higher than those in the corresponding normal controls (both P < 0.001). Enforced expression of miR-183 dramatically enhanced cell proliferation and G1/S transition, but inhibited cell apoptosis of leukemia cells. Bioinformatics prediction and luciferase reporter assay identified programmed cell death 6 (PDCD6) as a direct target gene of miR-183. Moreover, high serum miR-183 combined with low serum PDCD6 mRNA was significantly associated with French-American-British classification subtype M7 ( P = 0.01) and unfavorable karyotypes ( P = 0.006). Further multivariate analysis identified the combination of serum miR-183 and PDCD6 levels as an independent prognostic factor for both relapse-free and overall survivals. Functionally, re-introduction of PDCD6 markedly reversed the effects of miR-183 in cell cycle, proliferation and apoptosis of two leukemia cell lines. Conclusion: Combined serum miR-183 and PDCD6 mRNA may serve as a novel prognostic biomarker for pediatric AML. Interestingly, miR-183 may function as an oncogene and may enhance cell proliferation by targeting PDCD6, implying a potential therapeutic target for this malignancy. [ABSTRACT FROM AUTHOR]

Glioma is the most common type of primary malignant tumor in the central nervous system (CNS) with a high incidence and a high mortality rate, as well as an extremely low 5-year survival rate. As a class of small non-coding RNAs, microRNAs (miRNAs) may be closely involved in carcinogenesis and might also be connected with glioma diagnosis and prognosis. In this study, we aimed at investigating the expression level of microRNA-183 (miR-183) in 105 cases of glioma tissues of four World Health Organization (WHO) grades and 10 cases of normal brain tissues and its potential predictive and prognostic values in glioma. We found that the expression levels of miR-183 were significantly higher in glioma tissues than that in normal brain tissues, and also higher in high-grade gliomas (WHO grade III and IV) compared with low-grade gliomas (WHO grade I and II). The miR-183 expression level was classified as low or high according to the median value. High expression of miR-183 was found to significantly correlate with larger tumor size, higher WHO grade, and worse Karnofsky performance score (KPS). Kaplan-Meier survival analysis showed that patients with high miR-183 expression had worse overall survival (OS) and progression-free survival (PFS) than patients with low miR-183 expression. Moreover, univariate and multivariate analyses indicated that miR-183 expression level was an independent prognostic parameter of a patient's OS and PFS. In conclusion, our study indicated that miR-183 was upregulated in glioma, and that it may be used as a potential biomarker of poor prognosis in patients with glioma. [ABSTRACT FROM AUTHOR]

The microRNA (miR/miRNA)-182/183/96 cluster comprises miR-96, -182 and -183. The present study examined five previous microarray-based human colon cancer miR expression profiling studies and the expression of these three miRs was found to be upregulated in colon cancer tissues. Subsequently, in vitro assays were performed to determine the role of the miR-183/182/96 cluster in colon cancer cells. The results demonstrated that inhibiting miR-183, miR-182 or miR-96 with antisense oligonucleotide (ASO)-mimics inhibited the proliferation of colon cancer cells. Notably, further investigation revealed that inhibiting their expression simultaneously led to a more efficient reduction in cancer cell proliferation. These results suggested that miR-182/183/96, which resides in clusters in the genome, functioned synergistically in colon cancer and implied that co-expression of the miR cluster ASOs was efficient in reducing tumorigenesis, offering novel insight into the use of miRNAs in tumor therapy. [ABSTRACT FROM AUTHOR]

The aberrant expression of microRNA-183 (miRNA/ miR-183) has been found to be involved in numerous tumor types. However, the role of miR-183 in gastric cancer pathology is unclear and requires investigation. In the present study, the miR-183 expression levels of gastric cancer cell lines and tissues obtained from gastric cancer patients were measured by reverse transcription quantitative polymerase chain reaction analysis. The effect of miR-183 on gastric cancer cell proliferation and invasion was evaluated using MTT, colony formation and Transwell assays. The target of miR-183 was identified and confirmed using a luciferase activity assay. The results revealed that miR-183 was significantly downregulated in gastric cancer cells compared with GES-1 normal gastric epithelial cells. In addition, miR-183 was reduced in gastric cancer tissues compared with adjacent normal tissues. The ectopic expression of miR-183 significantly inhibited gastric cancer cell proliferation, colony formation and invasion. Bmi-1 was also confirmed as a downstream target of miR-183 in the gastric cancer cells by western blot analysis and luciferase activity assays. In conclusion, miR-183 is downregulated in gastric cancer cells and tissues, and inhibits gastric cancer cell proliferation and invasion by targeting Bmi-1. Therefore, targeting miR-183 may be a potential therapeutic strategy in gastric cancer patients. [ABSTRACT FROM AUTHOR]

MicroRNA-183 (miR-183) has been demonstrated to be a tumor suppressor miRNA in inhibition of migration and invasion of osteosarcoma by targeting an oncogene Ezrin. The aim of the present study was to determine the correlation of combined miR-183 and Ezrin mRNA expression with clinicopathologic features and prognosis in patients with osteosarcomas. Expressions of MiR-183 and Ezrin mRNA were both examined using quantitative real-time reverse transcriptase-polymerase chain reaction analysis in 68 specimens from patients with osteosarcomas. MiR-183 and Ezrin mRNA expression levels were, respectively, lower and higher in osteosarcoma tissues than those in noncancerous bone tissues significantly (both P < 0.001). Notably, the downregulation of miR-183 was negatively correlated with the upregulation of Ezrin mRNA in osteosarcoma tissues ( r = −0.66, P = 0.01). In addition, the combined miR-183 downregulation and Ezrin upregulation (miR-183-low/Ezrin-high) was significantly associated with high tumor grade ( P = 0.02), poor response to chemotherapy ( P = 0.01), positive metastasis ( P = 0.006) and recurrence ( P = 0.008). Moreover, miR-183/Ezrin expression and the status of metastasis were both found to be independent prognostic factors for overall survival ( P = 0.02 and 0.01, respectively) and disease-free survival (both P = 0.02). Our findings showed that the aberrant expression of miR-183 and its target gene Ezrin may play a crucial role in the development and progression of human osteosarcoma. More interestingly, the dysregulation of miR-183/Ezrin axis may be related to the prediction of aggressiveness and poor prognosis for patients with this lethal disease. [ABSTRACT FROM AUTHOR]

Abstract: Lung cancer is the leading cause of cancer death. However, the mechanism of lung cancer relapse and metastasis has been poorly elucidated. Recent researches have addressed the role of MicroRNAs (miRNAs) in mediating tumor metastasis. In the present study, we identified microRNA-183 (miR-183) as a potential metastasis-inhibitor. Expression level of miR-183 was reversely correlated with the metastatic potential of lung cancer cells. Furthermore, over-expression of miR-183 inhibited migration and invasion of lung cancer cells. Mechanistically, we identified VIL2-coding-protein Ezrin as a bona fide target of miR-183. We also found that miR-183 could regulate the expression of other genes involved in migration and invasion. Taken together, our findings demonstrated a new role and regulatory mechanism of miR-183 in controlling cancer metastasis. [Copyright &y& Elsevier]

Atherosclerosis is considered a chronic inflammatory disease, and macrophages function as important mediators in the development of atherogenesis. MicroRNA (miR)-183 is a small non-coding RNA that acts as a novel tumor suppressor and has recently been proposed to affect cardiac hypertrophy. However, the exact role and underlying mechanism of miR-183 in macrophage activation remain unknown. In the present study, miR-183 showed upregulated expression in atheromatous plaques and in bone marrow-derived macrophages (BMDMs) subjected to stimulation with oxidized low-density lipoproteins. Using a miR-183 loss-of-function strategy, it was demonstrated that miR-183 knockdown significantly increased resolving M2 macrophage marker expression but decreased proinflammatory M1 macrophage marker expression, as well as attenuated NF-κB activation. Moreover, decreased foam-cell formation accompanied by upregulation of genes involved in cholesterol efflux and downregulation of genes implicated in cholesterol influx was found in BMDMs transfected with a miR-183 inhibitor. Mechanistically, macrophage activation mediated by miR-183 silencing was partially attributed to direct upregulation of NR4A2 expression in BMDMs. Thus, the present study suggests that neutralizing miR-183 may be a potential therapeutic strategy for the treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]