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The purpose of this research was to provide light on the functional role that the long noncoding RNA SPACA6P‐AS plays in the biology of colorectal cancer (CRC). The presence of elevated SPACA6P‐AS expression in colorectal cancer tissues is linked to advanced stages of the disease as well as a decreased overall survival rate. It has been demonstrated through knockdown tests conducted on CRC cell lines that SPACA6P‐AS stimulates cell growth in both in vitro and in vivo settings. By acting as a competing endogenous RNA, SPACA6P‐AS is able to modulate the levels of miR‐339‐5p and promote the proliferation of colorectal cancer cells by way of the miR‐339‐5p/FAM167AFAM167A signaling axis. Based on these findings, SPACA6P‐AS is a promising candidate for both a prognostic marker and a therapeutic target in colorectal cancer. [ABSTRACT FROM AUTHOR]

Introduction: Pyroptosis can aggravate lung injury in sepsis. It has been reported that lncRNA SNHG16 can regulate the inflammatory response. However, the role and underlying mechanism of SNHG16 in sepsis-induced pyroptosis and lung injury remain unclear. Material and methods: To mimic septic lung injury in vitro, cells were treated with 1 µg/ml LPS. The Cell Counting Kit-8 (CCK-8) assay was performed to test cell viability. The lactate dehydrogenase (LDH) level was detected using a commercial kit. Interleukin (IL)-18 and IL-1 β secretion was tested using ELISA. Pyroptosis was investigated via flow cytometry. The relationship among SNHG16, miR-339-5p, and NLR family pyrin domain containing 1 (NLRP1) was explored using the dual luciferase assay. Results: LPS significantly upregulated the levels of SNHG16 and NLRP1 in BEAS-2B cells. In addition, LPS significantly induced pyroptosis in BEAS2B cells, while this phenomenon was reversed by SNHG16 silencing. SNHG16 could bind with miR-339-5p, and NLRP1 was found to be the downstream mRNA of miR-339-5p. SNHG16 silencing significantly abolished the LPS-induced upregulation of NLRP1 through miR-339-5p downregulation. The upregulation of miR-339-5p inhibited the pro-apoptotic effect of LPS on BEAS-2B cells, which was abolished by NLRP1 overexpression. Furthermore, the anti-pyroptotic effect of SNHG16 siRNA was abolished by NLRP1 upregulation. Conclusions: SNHG16 silencing reversed LPS-induced pyroptosis in BEAS-2B cells via miR-339-5p/NLRP1 axis mediation. Our study might shed new light on exploring therapeutic strategies for the treatment of septic lung injury. [ABSTRACT FROM AUTHOR]

In this study, we aimed to investigate cytoplasmic maturation and miRNA expression of mature oocytes cultured in porcine follicular fluid exosomes. We also examined the effect of miR-339-5p on oocyte maturation. Twenty eight differentially expressed miRNAs were detected using miRNA-seq. We then transfected cumulus oocyte complexes with miR-339-5p mimics and inhibitor during culture. The results showed that exosomes increased endoplasmic reticulum levels and the amount of lipid droplets, and decreased ROS levels, lipid droplet size, and percentage of oocytes with abnormal cortical granule distribution. Overexpressing miR-339-5p significantly decreased cumulus expansion genes, oocyte maturation-related genes, target gene proline/glutamine-rich splicing factor (SFPQ), ERK1/2 phosphorylation levels, oocyte maturation rate, blastocyst rate, and lipid droplet number, but increased lipid droplet size and the ratio of oocytes with abnormal cortical granule distribution. Inhibiting miR-339-5p reversed the decrease observed during overexpression. Mitochondrial membrane potential and ROS levels did not differ significantly between groups. In summary, exosomes promote oocyte cytoplasmic maturation and miR-339-5p regulating ERK1/2 activity through SFPQ expression, thereby elevating oocyte maturation and blastocyst formation rate in vitro. • This study examined the mechanisms behind enhanced in vitro oocyte maturation in pigs with follicular fluid exosomes. • MiRNA sequencing experiments demonstrated that miR-339-5p was differentially expressed between treatment groups. • MiR-339-5p regulated the ERK1/2 pathway through SFPQ and improved various measures of oocyte maturation. [ABSTRACT FROM AUTHOR]

Preventing and treating avascular necrosis at the distal end of the flaps are critical to surgery success, but current treatments are not ideal. A recent study shows that apoptotic bodies (ABs) generated near the site of apoptosis can be taken up and promote cell proliferation. The study reveals that ABs derived from fibroblast‐like cells in the subcutaneous connective tissue (FSCT cells) of skin flaps promoted ischaemic flap survival. It is also found that ABs inhibited cell death and oxidative stress and promoted M1‐to‐M2 polarization in macrophages. Transcriptome sequencing and protein level testing demonstrated that ABs promoted ischaemic flap survival in endothelial cells and macrophages by inhibiting ferroptosis via the KEAP1‐Nrf2 axis. Furthermore, microRNA (miR) sequencing data and in vitro and in vivo experiments demonstrated that ABs inhibited KEAP1 by delivering miR‐339‐5p to exert therapeutic effects. In conclusion, FSCT cell‐derived ABs inhibited ferroptosis, promoted the macrophage M1‐to‐M2 transition via the miR‐339‐5p/KEAP1/Nrf2 axis and promoted ischaemic flap survival. These results provide a potential therapeutic strategy to promote ischaemic flap survival by administering ABs. [ABSTRACT FROM AUTHOR]

Background: Liver cancer has a high incidence and mortality rate worldwide, and there is an urgent need to identify new therapeutic strategies and predictive targets to improve the clinical outcomes of advanced liver cancer. Ferroptosis holds promise as a novel strategy for cancer therapy. Epigenetic dysregulation is a hallmark of cancer, and noncoding RNAs are tightly involved in cell fate determination. Therefore, we aimed to identify a novel ferroptosis regulator from aberrantly expressed microRNAs that may serve as a novel biomarker and therapeutic target for liver cancer. Methods: The expression signature and prognostic value of miR-339 was assessed using TCGA data set. The role of miR-339/ATG7/FTH1 axis in liver cancer cells were evaluated through growth curve, colony formation, 7-AAD staining. The role of miR-339 in regulation of ferroptosis was determined by immunofluorescence staining, flow cytometry, and Elisa kits. Results: Here, we showed that miR-339 is aberrantly overexpressed in patients with liver cancer. In addition, miR-339 inhibition dramatically suppresses liver cancer progression. Furthermore, miR-339 silencing drives cell death and inhibits liver cancer progression, indicating that miR-339 may serve as a novel ferroptosis suppressor. Mechanistically, we demonstrated that miR-339 targets ATG7 to facilitate the autophagic degradation of FTH1 and prevent ferroptosis in liver cancer cells. Conclusions: We provide important evidence that the miR-339 inhibition activates of the autophagy pathway to promote ferroptosis by degrading FTH1 in liver cancer cells. We found that miR-339 regulates the balance between ferroptosis and autophagy in liver cancer cells. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome virus (PRRSV) is a variable virus, whose spread cannot be totally stopped by vaccination. PRRSV infection results in abortion and respiratory symptoms in pregnant pigs. One crucial component of the anti-viral infection strategy is microRNA (miRNA), a class of multifunctional small molecules. It is unknown whether miR-339-5p can specifically target the PRRSV gene and prevent the virus from replicating, despite the fact that miR-339-5p is markedly up-regulated during the PRRSV infection. In this pursuit, the present study revealed that the two PRRSV areas targeted by miR-339-5p were PRRSV nsp2-3378 to 3403 and PRRSV nsp2-3112 to 3133 using the miRanda program. Dual luciferase reporter assays showed that the miR-339-5p target region of the PRRSV gene sequence exhibited 100% homology and was highly conserved. Furthermore, the ability of miR-339-5p to target PRRSV gene areas was verified. It was found that the overexpression of miR-339-5p markedly reduced the PRRSV replication through PRRSV infection trials. The precursor sequence of ssc-miR-339-5p was amplified using the DNA of pig lung tissue as a template in order to create a fragment of 402 bp of porcine-derived miR-339-5p precursor sequence, which was then used to produce the eukaryotic expression plasmid of miR-339-5p. In conclusion, miR-339-5p can target the specific PRRSV gene areas and prevent PRRSV replication, offering fresh perspectives for the creation of medications that combat the PRRSV infection. [ABSTRACT FROM AUTHOR]

Dongsheng Zhu,1,* Zhitao Zhu,2,* Han Qi3 1Department of Pediatric Surgery, the First People’s Hospital of Lianyungang, Affiliated to Xuzhou Medical University, Lianyungang, Jiangsu, 222000, People’s Republic of China; 2Department of Radiology, the Second People’s Hospital of Lianyungang, Lianyungang, Jiangsu, 222000, People’s Republic of China; 3Department of Emergency Surgery, the Second People’s Hospital of Lianyungang, Lianyungang, Jiangsu, 222000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongsheng Zhu, Email zhudongsheng@tmu.edu.cnObjective: Long non-coding RNA plays an important role in osteogenic differentiation. Nuclear enriched abundant transcript 1 (NEAT1) has been revealed to promote osteogenic differentiation in human bone marrow mesenchymal stem cells (hBMSCs), but the underlying regulatory mechanism remains unknown in acute suppurative osteomyelitis of children.Methods: Osteogenic medium (OM) was used to induce osteogenic differentiation. Quantitative real-time PCR and Western blotting were used to evaluate gene expression. The effects of NEAT1, microRNA 339– 5p (miR-339-5p), and salmonella pathogenicity island 1 (SPI1) on osteogenic differentiation were assessed in vitro using alizarin red S staining assays and alkaline phosphatase activity. Interactions between NEAT1, miR-339-5p, and SPI1 were identified using immunoprecipitation, luciferase reporter assays, and chromatin immunoprecipitation.Results: During osteogenic differentiation, expression of NEAT1 was up-regulated in hBMSCs, and miR-339-5p level was down during osteogenic differentiation. Knockdown of NEAT1 reduced the osteogenic differentiation of hBMSCs, and down-regulation of miR-339-5p may counteract the effect of NEAT1 silencing. SPI1 was a target of miR-339-5p by luciferase reporter assay and was also a transcription factor of NEAT1 by chromatin immunoprecipitation. A positive NEAT1-miR-339-5p-SPI1 feedback loop was found to be present during osteogenic differentiation in hBMSCs.Conclusion: It was the first study to reveal that the NEAT1-miR-339-5p-SPI1 feedback loop can promote osteogenic differentiation in hBMSCs and shed a new light on the role of NEAT1 during osteogenic differentiation.Keywords: NEAT1, miR-339-5p, SPI1, osteogenic differentiation

Background: Liver injury in pregnancy significantly impacts the physical and mental health of pregnant women, and finding a potential therapeutic target is crucial for early prediction and improving adverse pregnancy outcomes. This study aims to examine the relationship between miR-339-5p expression and early diagnosis and pregnancy outcomes in patients experiencing liver injury in pregnancy. Methods: A retrospective study of 63 patients with liver injury in pregnancy. The expression of miR-339-5p in plasma of patients with liver health and liver injury in pregnancy was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The value of miR-339-5p in the diagnosis and pregnancy outcomes of patients with liver injury in pregnancy was evaluated by receiver operating characteristic (ROC) and Cox regression analysis. Results: The alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acids (TBA), total bilirubin (TBIL) levels and miR-339-5p expression of patients in the intrahepatic cholestasis of pregnancy (ICP), hemolysis, elevated liver enzymes, and low platelet count (HELLP) and acute fatty liver of pregnancy (AFLP) groups, respectively, were statistically significant compared with those in the healthy control (HC) group (p < 0.05). MiR-339-5p expression was significantly lower in patients with liver injury in pregnancy compared to healthy individuals. This difference could be used to distinguish between healthy individuals and those with liver injury in pregnancy (area under the curve (AUC) = 0.897, 95% confidence interval (95% CI) = 0.843–0.951). In addition, ALT (r = –0.686), AST (r = –0.699) and TBA (r = –0.706) were highly negatively correlated with miR-339-5p expression, respectively. MiR-339-5p can be used as a biomarker of liver injury in pregnancy to predict adverse pregnancy outcomes. Conclusions: MiR-339-5p could potentially be used as a potential molecular marker for early diagnosis of liver injury in pregnancy and the prediction of adverse pregnancy outcomes.

Objective To study the effect of lncRNA UNC5B-AS1 targeting miR-339-5p on the proliferation and apoptosis of lung cancer cells and its molecular mechanism. Methods The human lung adenocarcinoma cell line A549 was cultured in vitro, and si-NC, si-UNC5B-AS1, miR-NC, miR-339-5p mimics, si-UNC5B-AS1 and anti-miR-NC, si-UNC5B-AS1 and anti-miR-339-5p were transfected into A549 cells respectively. Real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the expression of UNC5B-AS1 and miR-339-5p in lung cancer tissues and in adjacent tissues; Cell counting kit (CCK-8) was used to detecte cell proliferation; The targeted regulation relationship between UNC5B-AS1 and miR-339-5p was examined by dual luciferase reporter gene experiment; Western blot was used to detect the expression of cyclin D1 (cyclin D1), p21 protein lymphoma-2(Bcl-2), and B lymphoma-2 related protein (Bax). Results Compared with adjacent tissues, the expression level of UNC5B-AS1 in lung cancer tissue was significantly increased (P＜0.05), and the expression level of miR-339-5p was significantly decreased(P＜0.05). Compared with the si-NC group, the cell viability of the si-UNC5B-AS1 group was significantly reduced (P＜0.05), the apoptosis rate was significantly higher(P＜0.05). Compared with the miR-NC group, the cell viability of the miR-339-5p group was significantly reduced (P＜0.05), and the apoptosis rate was significantly increased(P＜0.05). Compared with the (si-UNC5B-AS1+anti-miR-NC)group, the cell viability of the (si-UNC5B-AS1+anti-miR-339-5p) group was significantly increased (P＜0.05); the apoptosis rate was significantly reduced (P＜0.05). Conclusions Interference with UNC5B-AS1 promotes apoptosis and inhibits cell proliferation of human lung adenocarcinoma cancer cell line A549 by up-regulating the expression of miR-339-5p.

O: BJECTIVES: Circular RNAs (circRNAs) are known to be associated with the progression of gestational diabetes mellitus (GDM). Thus, the objective of this study was to unveil the influnce and potential mechanism of hsa&#95;circ&#95;0002768 in GDM. M: ATERIAL AND: METHODS: Levels of hsa&#95;circ&#95;0002768 were quantified by RT-qPCR. Placental hsa&#95;circ&#95;0002768 levels were analyzed after pregnancies. Trophoblast cell (HTR-8/SVneo) functions, including oxidative stress, mitochondrial dysfunction, cell viability, autophagy, and invasion, were evaluated upon hsa&#95;circ&#95;0002768 knockdown. Finally, the downstream miRNA for hsa&#95;circ&#95;0002768 was investigated. RESULTS: Hsa&#95;circ&#95;0002768 levels increased as high glucose-induced, and in GDM placenta. In vitro experiments showed that hsa&#95;circ&#95;0002768 knockdown positively regulated trophoblast oxidative stress and mitochondrial functions, thus inducing cell viability and invasion, but inhibiting autophagy. miR-339-5p was a downstream molecular for hsa&#95;circ&#95;0002768, which targeted to TLE3. CONCLUSIONS: This study reveals a physiological role for hsa&#95;circ&#95;0002768 during GDM.

Chronic glomerulonephritis (CGN) is a disease occurred in glomeruli. The mechanism of CGN is regarded to be involved in a range of inflammatory responses. MicroRNA-339-5p (miR-339-5p) has been reported to be involved in inflammatory responses in many diseases. However, the role of miR-339-5p in CGN remains unclear. The purpose of this study was to investigate the role of miR-339-5p in lipopolysaccharide (LPS)-induced nephritis injury in vitro. The real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and western blot (WB) were used to detect the expression of miR-339-5p and Syk/Ras/c-Fos pathway. Double luciferase was performed to identify targeted binding of miR-339-5p to Syk. Cell counting kit-8 (CCK-8) and flow cytometry were used to observe cell viability and cell cycle. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the concentrations of inflammatory cytokines IL-1β, IL-10, IL-6, and TNF-α. Lipopolysaccharide (LPS) could increase HBZY-1 (rat mesangial cells) cell viability, decrease the G2 phase, and promote cell proliferation and accelerate inflammatory cytokine. However, overexpression of miR-339-5p could inhibit LPS-induced HBZY-1 cell viability, decrease the expression of Syk/Ras/c-Fos signaling pathway, downregulate the expression level of inflammatory cytokines, increase the G2 phase, and inhibit cell proliferation. miR-339-5p could inhibit the proliferation and inflammation of the rat mesangial cells through regulating Syk/Ras/c-Fos signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract Background Small nucleolar RNA host gene (SNHG) long noncoding RNAs (lncRNAs) are frequently dysregulated in human cancers and involved in tumorigenesis and progression. SNHG17 has been reported as a candidate oncogene in several cancer types, however, its regulatory role in colorectal cancer (CRC) is unclear. Methods SNHG17 expression in multiple CRC cohorts was assessed by RT-qPCR or bioinformatic analyses. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell mobility and invasiveness were assessed by Transwell assays. Tumor xenograft and metastasis models were applied to confirm the effects of SNHG17 on CRC tumorigenesis and metastasis in vivo. Immunohistochemistry staining was used to measure protein expression in cancer tissues. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of SNHG17 in CRC. Results Using multiple cohorts, we confirmed that SNHG17 is aberrantly upregulated in CRC and correlated with poor survival. In vitro and in vivo functional assays indicated that SNHG17 facilitates CRC proliferation and metastasis. SNHG17 impedes PES1 degradation by inhibiting Trim23-mediated ubiquitination of PES1. SNHG17 upregulates FOSL2 by sponging miR-339-5p, and FOSL2 transcription activates SNHG17 expression, uncovering a SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop. Conclusions We identified SNHG17 as an oncogenic lncRNA in CRC and identified abnormal upregulation of SNHG17 as a prognostic risk factor for CRC. Our mechanistic investigations demonstrated, for the first time, that SNHG17 promotes tumor growth and metastasis through two different regulatory mechanisms, SNHG17-Trim23-PES1 axis and SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop, which may be exploited for CRC therapy.

MicroRNAs (miRNAs) regulate multiple biological processes and participate in various cardiovascular diseases. This study aims to investigate the role of miR‐339‐5p in cardiomyocyte hypertrophy and the involved mechanism. Neonatal rat cardiomyocytes (NRCMs) were cultured and stimulated with isoproterenol (ISO). The hypertrophic responses were monitored by measuring the cell surface area and expression of hypertrophic markers including β‐myosin heavy chain (β‐MHC) and atrial natriuretic factor (ANF). Bioinformatic prediction tools and dual‐luciferase reporter assay were performed to identify the target gene of miR‐339‐5p. Quantitative real‐time polymerase chain reaction and western blot analysis were used to determine the levels of miR‐339‐5p and its downstream effectors. Our data showed that miR‐339‐5p was upregulated during cardiomyocyte hypertrophy triggered by ISO. MiR‐339‐5p overexpression resulted in enlargement of cell size and increased the levels of hypertrophic markers. In contrast, inhibition of miR‐339‐5p significantly attenuated ISO‐induced hypertrophic responses of NRCMs. Valosin‐containing protein (VCP), a suppressor of cardiac hypertrophy via inhibiting mechanistic target of rapamycin (mTOR) signaling, was validated as a target of miR‐339‐5p. MiR‐339‐5p suppressed VCP protein expression, leading to elevated phosphorylation of mTOR and ribosomal protein S6 kinase (S6K). VCP depletion activated the mTOR/S6K cascade and could compromise the anti‐hypertrophic effects of miR‐339‐5p inhibitor. Additionally, the hypertrophic responses caused by miR‐339‐5p was alleviated in the presence of mTOR inhibitor rapamycin. In conclusion, our research revealed that miR‐339‐5p promoted ISO‐induced cardiomyocyte hypertrophy by targeting VCP to activate the mTOR signaling, suggesting a promising therapeutic intervention by interfering miR‐339‐5p. [ABSTRACT FROM AUTHOR]

Background: Small nucleolar RNA host gene (SNHG) long noncoding RNAs (lncRNAs) are frequently dysregulated in human cancers and involved in tumorigenesis and progression. SNHG17 has been reported as a candidate oncogene in several cancer types, however, its regulatory role in colorectal cancer (CRC) is unclear. Methods: SNHG17 expression in multiple CRC cohorts was assessed by RT-qPCR or bioinformatic analyses. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell mobility and invasiveness were assessed by Transwell assays. Tumor xenograft and metastasis models were applied to confirm the effects of SNHG17 on CRC tumorigenesis and metastasis in vivo. Immunohistochemistry staining was used to measure protein expression in cancer tissues. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of SNHG17 in CRC. Results: Using multiple cohorts, we confirmed that SNHG17 is aberrantly upregulated in CRC and correlated with poor survival. In vitro and in vivo functional assays indicated that SNHG17 facilitates CRC proliferation and metastasis. SNHG17 impedes PES1 degradation by inhibiting Trim23-mediated ubiquitination of PES1. SNHG17 upregulates FOSL2 by sponging miR-339-5p, and FOSL2 transcription activates SNHG17 expression, uncovering a SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop. Conclusions: We identified SNHG17 as an oncogenic lncRNA in CRC and identified abnormal upregulation of SNHG17 as a prognostic risk factor for CRC. Our mechanistic investigations demonstrated, for the first time, that SNHG17 promotes tumor growth and metastasis through two different regulatory mechanisms, SNHG17-Trim23-PES1 axis and SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop, which may be exploited for CRC therapy. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) and Multiple System Atrophy (MSA) are progressive neurodegenerative diseases with overlap of symptoms in early stages of disease. No reliable biomarker exists and the diagnosis is mainly based on clinical features. Several studies suggest that miRNAs are involved in PD and MSA pathogenesis. Our goal was to study two serum circulating microRNAs (miR-96-5p and miR-339-5p) as novel biomarkers for the differential diagnosis between PD and MSA. Serum samples were obtained from 51 PD patients, 52 MSA patients and 56 healthy controls (HC). We measured levels of miRNAs using quantitative PCR and compared the levels of miR-96-5p and miR-339-5p among PD, MSA and HC groups using a one-way analysis of variance. Correlations between miRNA expression and clinical data were calculated using Pearson's rho test. We used the miRTarBase to detect miRNA targets and STRING to evaluate co-expression relationship among target genes. MiR-96-5p was significantly increased in MSA patients compared with HC (Fold change (fc): 3.6; p = 0.0001) while it was decreased in PD patients compared with HC (Fold change: 4; p = 0.0002). Higher miR-96-5P levels were directly related to longer disease duration in MSA patients. We observed a significant increase of miR-339-5p in MSA patients compared with PD patients (fc: 2.5; p = 0.00013). miR-339-5p was increased in MSA patients compared with HC (fc: 2.4; p = 0.002). We identified 32 target genes of miR-96-5p and miR-339-5p, some of which are involved in neurodegenerative diseases. The study of those miRNAs could be useful to identify non-invasive biomarkers for early differential diagnosis between PD and MSA.

Parkinson's disease (PD) and Multiple System Atrophy (MSA) are progressive neurodegenerative diseases with overlap of symptoms in early stages of disease. No reliable biomarker exists and the diagnosis is mainly based on clinical features. Several studies suggest that miRNAs are involved in PD and MSA pathogenesis. Our goal was to study two serum circulating microRNAs (miR-96-5p and miR-339-5p) as novel biomarkers for the differential diagnosis between PD and MSA. Serum samples were obtained from 51 PD patients, 52 MSA patients and 56 healthy controls (HC). We measured levels of miRNAs using quantitative PCR and compared the levels of miR-96-5p and miR-339-5p among PD, MSA and HC groups using a one-way analysis of variance. Correlations between miRNA expression and clinical data were calculated using Pearson's rho test. We used the miRTarBase to detect miRNA targets and STRING to evaluate co-expression relationship among target genes. MiR-96-5p was significantly increased in MSA patients compared with HC (Fold change (fc): 3.6; p = 0.0001) while it was decreased in PD patients compared with HC (Fold change: 4; p = 0.0002). Higher miR-96-5P levels were directly related to longer disease duration in MSA patients. We observed a significant increase of miR-339-5p in MSA patients compared with PD patients (fc: 2.5; p = 0.00013). miR-339-5p was increased in MSA patients compared with HC (fc: 2.4; p = 0.002). We identified 32 target genes of miR-96-5p and miR-339-5p, some of which are involved in neurodegenerative diseases. The study of those miRNAs could be useful to identify non-invasive biomarkers for early differential diagnosis between PD and MSA. [ABSTRACT FROM AUTHOR]

Hui Zeng,1 Jiaping Zheng,1 Song Wen,1 Jun Luo,1 Guoliang Shao,1 Yongjun Zhang2 1Department of Interventional Radiology, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang, P.R. China; 2Department of Integration of Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang, P.R. China Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality worldwide, however, the prognosis for HCC remains unsatisfactory. This study aimed to explore the role of miR-339-5p in HCC.Methods: We first used quantitative real-time PCR to examine the level of miR-339-5p in HCC tissues. Then we further adopted Western blotting assay, CCK8, cell invasion assays, apoptosis detection assay, and luciferase assay to analyze how it mediate the development of HCC.Results: We found that miR-339 is significantly decreased in primary HCC tissues. Overexpression of miR-339 in HCC cells remarkably suppressed proliferation and invasion and induced apoptosis. However, silencing miR-339 in HCC cells promoted proliferation and invasion, and reduced apoptosis. Moreover, we demonstrated that ZNF689 is a target of miR-339 and there is a negative correlation between miR-339 and ZNF689 expression in the HCC tissues. Overexpression of ZNF689 in miR-339-overexpressing HCC cells partially antagonized the inhibitory effects of miR-339. Conclusion: Our study revealed that miR-339 inhibits HCC growth through targeting oncoprotein ZNF689 and restoration of miR-339 might be feasible therapeutic strategy for HCC treatment. Keywords: miR-339-5p, HCC, ZNF689, treatment, proliferation

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department 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.)

Background: Long-chain non-coding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) is reportedly overexpressed in malignant tumors, but its regulatory role in human ovarian cancer (OC) is not fully understood. Methods: A qRT-PCR assay was carried out to detect the level of SNHG3 in OC tissues, serum and cells, a CCK-8 assay to measure the proliferation of OC cells, a transwell assay to measure the invasion and migration of OC cells, and a flow cytometry to detect the cell cycle distribution and apoptosis rate of OC cells. In addition, in vivo experiment was also conducted to determine the effect of SNHG3 on the growth of OC cells. Results: SNHG3 was overexpressed in OC tissues, serum, and cells, and the overexpression in serum indicated a poor prognosis of patients. It was also found that knockdown of SNHG3 could inhibit the malignant phenotypes of OC cells, cause G1/G0 cell cycle arrest, and intensify apoptosis. Furthermore, in in vitro experiments, the growth ability of OC cells was inhibited under knockdown of SNHG3. Assays for relationship verification showed that SNHG3 regulated the expression of miR-339-5p and the canonical transient receptor potential 3 (TRPC3), and the rescue experiment revealed that co-transfection of si-SNHG3+miR-339-5p-inhibitor or si-SNHG3+pcDNA3.1-TRPC3 could reverse the effects of knockdown of SNHG3 on the biological behavior of OC cells. Conclusion: SNHG3 can be adopted as a marker for diagnosis and prognosis evaluation of OC and it plays a role in the progression of OC by enabling the miR-339-5p sponge to regulate TRPC3 expression. [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.)

The long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) has been recognized as a tumor oncogene involved in the development of multiple cancers. However, the function of NEAT1 and its molecular mechanism in osteosarcoma (OS) remain unclear. First, we detected the NEAT1 expression in OS cell lines by performing quantitative reverse‐transcription polymerase chain reaction. Next, the effects of NEAT1 on OS cell growth, apoptosis, migration, and invasion were tested by lentivirus‐mediated downregulation. We observed that inhibition of NEAT1 restrained OS cell progression greatly. Interestingly, in the last few years, increasing studies have shown that some lncRNAs can act as miRNA sponges and reduce the amount of the same. Here, we found that NEAT1 can modulate OS development via sponging miR‐339‐5p. MiR‐339‐5p was significantly decreased in OS cells, and its overexpression can remarkably repress the OS proliferation. These results indicated that NEAT1 could function as a tumor oncogene in OS by inhibiting miR‐339‐5p in vitro. Then, the following assays validated that transforming growth factor β1 (TGF‐β1) can act as a functional target of miR‐339‐5p in OS cells. Finally, we indicated that NEAT1 could mediate TGF‐β1 expression by competitively sponging miR‐339‐5p. NEAT1 induced OS cell proliferation and cell mobility by binding to miR‐339‐5p and increasing TGF‐β1 in OS. It was demonstrated in our study that lncRNA NEAT1 could impede miR‐339‐5p expression to maintain the expression of TGF‐β1, which led to the development of OS. Our findings implied that the novel identified NEAT1/miR‐339‐5p/TGF‐β1 axis might be a new molecular pathway or therapeutic target for OS diagnosis and treatment. It was the first time to report a novel role of nuclear enriched abundant transcript 1 (NEAT1)/miR‐339‐5p/transforming growth factor β1 (TGF‐β1) axis in osteosarcoma (OS). We observed that NEAT1 was elevated in OS cells and NEAT1 silence could inhibit OS cell growth, migration, and invasion. In addition, miR‐339‐5p was downregulated in OS cells, and miR‐339‐5p mimics could inhibit OS development. For another, TGF‐β1 was increased in OS cells, which could act as a direct target of miR‐339‐5p. [ABSTRACT FROM AUTHOR]

Non‐small‐cell carcinoma (NSCLC) is the most common cancer along with high mortality rate worldwide. In the present study, our data showed that lncRNA MAF BZIP Transcription Factor G Antisense RNA 1 (MAFG‐AS1) was over‐expressed in NSCLC tissues and cell lines. Overexpression of MAFG‐AS1 promoted the migration, invasion and enhanced epithelial‐mesenchymal transition (EMT) of NSCLC cell. In addition, miR‐339‐5p was predicted to be a target of MAFG‐AS1 and the level of miR‐339‐5p was down‐regulated in NSCLC. Over‐expression of MAFG‐AS1 significantly decreased the level of miR‐339‐5p in NSCLC cell. Moreover, the matrix metalloproteinase 15 (MMP15) was identified to be a target of miR‐339‐5p. The level of MMP15 was negatively regulated by miR‐339‐5p whereas positively controlled by MAFG‐AS1. In addition, up‐regulation of miR‐339‐5p neutralized the promoting impact of MAFG‐AS1 on the migration, invasion and EMT of NSCLC cell. Finally, the xenograft model suggested that MAFG‐AS1 promoted the metastasis of NSCLC cell in vivo. Altogether, we proved that MAFG‐AS1‐miR‐339‐5p‐MMP15 axis might be a promising therapeutic target for the treatment of patients with NSCLC. [ABSTRACT FROM AUTHOR]

Esophageal cancer is one of the most malignant gastrointestinal malignancies. Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China. In recent years, with developments in basic medicine, it has been demonstrated that the abnormal expression of circular RNA (circRNA) plays an important role in the progression and prognosis of ESCC. This study explored the role and downstream molecular mechanisms of circ_0046534 in ESCC. We identified circ_0046534, which was found to be highly expressed in ESCC tissues and cells. Moreover, the downregulation of circ_0046534 inhibited the proliferation, migration and invasion of ESCC cells and the growth and metastasis of ESCC tumours in vivo. Dual-luciferase reporter assays showed that circ_0046534 sponged miR-339-5p and inhibited the expression of miR-339-5p. Furthermore, MMP2 was identified to be a direct target of miR-339-5p through bioinformatics analysis. In addition, the knockdown of circ_0046534 inhibited the expression of the downstream target gene matrix metalloproteinase 2 (MMP2) by releasing the adsorption of miR-339-5p. Taken together, this study demonstrated that silencing circ_0046534 inhibited the growth and metastasis of ESCC through the miR-339-5p/MMP2 pathway. Circ_0046534 is expected to serve as a new biomarker and target for ESCC and provide a new direction for its diagnosis and treatment. [Display omitted] • High expression of hsa_circ_0046534 in ESCC accelerated the metastasis and growth of ESCC through miR-339-5p/MMP2 signaling pathway. [ABSTRACT FROM AUTHOR]

Glycine-histidine-lysine (GHK) is a human tripeptide that enhances wound healing, exerts neuroprotective effects against neurodegenerative disease, and improves tissue regeneration. This study examined whether GHK can alleviate injury due to intracerebral hemorrhage (ICH). Briefly, adult Wistar rats in GHK pretreatment groups were injected with GHK (1 or 10 mg/kg, i.p.) every 24 h for 3 days. Water content and intact neurons were detected in the rats 3 days after ICH, and the neurological deficit scores were examined in the rats at 4, 24, 72, and 168 h after ICH. Apoptosis was evaluated via caspase-3 immunohistochemistry, Nissl staining, and TUNEL assay. We also examined the effect of GHK on the expression of related proteins in SH-SY5Y cells via Western blotting. The expression of miR-339-5p was examined via real-time polymerase chain reaction analyses. GHK improved neurological deficits, reduced water content in the brain and inhibited neuronal apoptosis in ICH rats. It also prevented the apoptosis of SH-SY5Y cells with hemin treatment. Furthermore, GHK downregulated miR-339-5p expression, and overexpression of miR-339-5p partially reversed the anti-apoptotic effects of GHK in SH-SY5Y cells. Our findings suggest that the p38 MAPK pathway is involved in the GHK-induced downregulation of miR-339-5p, and that the miR-339-5p/VEGFA axis plays a role in preventing neuronal apoptosis following ICH injury. These findings indicate that GHK may represent a novel therapeutic strategy for ICH.

Emerging evidence discloses the involvement of calcium channel protein in the pathological process of liver diseases. Transient receptor potential cation channel subfamily C member 3 (TRPC3), a ubiquitously expressed non-selective cation channel protein, controls proliferation, inflammation, and immune response via operating calcium influx in various organs. However, our understanding on the biofunction of hepatic TRPC3 is still limited. The present study aims to clarify the role and potential mechanism(s) of TRPC3 in alcohol-associated liver disease (ALD). We recently found that TRPC3 expression plays an important role in the disease process of ALD. Alcohol exposure led to a significant reduction of hepatic TRPC3 in patients with alcohol-related hepatitis (AH) and ALD models. Antioxidants (N-acetylcysteine and mitoquinone) intervention improved alcohol-induced suppression of TRPC3 via a miR-339-5p-involved mechanism. TRPC3 loss robustly aggravated the alcohol-induced hepatic steatosis and liver injury in mouse liver; this was associated with the suppression of Ca 2+ /calmodulin-dependent protein kinase kinase 2 (CAMKK2)/AMP-activated protein kinase (AMPK) and dysregulation of genes related to lipid metabolism. TRPC3 loss also enhanced hepatic inflammation and early fibrosis-like change in mice. Replenishing hepatic TRPC3 effectively reversed chronic alcohol-induced detrimental alterations in ALD mice. Briefly, chronic alcohol exposure-induced TRPC3 reduction contributes to the pathological development of ALD via suppression of the CAMKK2/AMPK pathway. Oxidative stress-stimulated miR-339-5p upregulation contributes to alcohol-reduced TRPC3. TRPC3 is the requisite and a potential target to defend alcohol consumption-caused ALD., Competing Interests: The authors declare that no conflict of interest exists., (© The Author(s) 2023. Published by Oxford University Press on behalf of Higher Education Press.)

Lung adenocarcinoma (LA) is a common non-small cell lung cancer, but effective biomarkers to diagnose early LA are still lacking. Increasing evidence has indicated that the dysregulation of microRNAs (miRNAs) play crucial roles in LA progression. miR-339-5p has been recently confirmed to exert crucial functions in various cancers. Nevertheless, molecular mechanisms and effects of miR-339-5p on LA development still remain vague. In the present research, miR-339-5p expression was downregulated in human LA tissues. miR-339-5p overexpression in LA cells could remarkably suppress the LA cell invasion and migration. In addition, further studies indicated that miR-339-5p overexpression downregulated both the B-cell lymphoma 6 (BCL6) mRNA and protein expressions by targeting the BCL6 3′-UTR directly. Moreover, BCL6 knockdown could partially lessen the function of miR-339-5p in LA invasion and migration. In conclusion, the present data identified miR-339-5p as a novel LA suppressor which exerted its functions partly by negatively regulating BCL6. [ABSTRACT FROM AUTHOR]

Glycine-histidine-lysine (GHK) is a human tripeptide that enhances wound healing, exerts neuroprotective effects against neurodegenerative disease, and improves tissue regeneration. This study examined whether GHK can alleviate injury due to intracerebral hemorrhage (ICH). Briefly, adult Wistar rats in GHK pretreatment groups were injected with GHK (1 or 10 mg/kg, i.p.) every 24 h for 3 days. Water content and intact neurons were detected in the rats 3 days after ICH, and the neurological deficit scores were examined in the rats at 4, 24, 72, and 168 h after ICH. Apoptosis was evaluated via caspase-3 immunohistochemistry, Nissl staining, and TUNEL assay. We also examined the effect of GHK on the expression of related proteins in SH-SY5Y cells via Western blotting. The expression of miR-339-5p was examined via real-time polymerase chain reaction analyses. GHK improved neurological deficits, reduced water content in the brain and inhibited neuronal apoptosis in ICH rats. It also prevented the apoptosis of SH-SY5Y cells with hemin treatment. Furthermore, GHK downregulated miR-339-5p expression, and overexpression of miR-339-5p partially reversed the anti-apoptotic effects of GHK in SH-SY5Y cells. Our findings suggest that the p38 MAPK pathway is involved in the GHK-induced downregulation of miR-339-5p, and that the miR-339-5p/VEGFA axis plays a role in preventing neuronal apoptosis following ICH injury. These findings indicate that GHK may represent a novel therapeutic strategy for ICH. [ABSTRACT FROM AUTHOR]

Background Many studies have shown that differentially expressed miRs in body fluids can serve as biomarkers in non-invasive detection of the cancers. However, the clinical significance of plasma miRs in the diagnosis of lung adenocarcinoma (LA) is still not clear. Therefore, we examined the LA-specific miRs in plasma, which could be utilized to diagnosis and monitor LA in routine clinical practice. Methods Twenty-eight LA cases and twenty-eight healthy controls were recruited to our study. MiRs differential expression in plasma was measured by miRNA Microarray assay and revalidated by using qRT-PCR based absolute quantification methods The diagnostic power of circulating miRs in LA was evaluated using the receiver operating characteristics (ROC) curves and the area under the ROC curves (AUC). Results Tumor tissues and plasma levels of miR-339-5p were significantly down-regulated in LA patients compared with those in the control group, whereas the levels of miR-21 in LA patients were significantly higher than control group. ROC analysis showed that miR-339-5p and miR-21 could distinguish LA patients from healthy controls with high AUC (0.900 and 0.880, respectively), sensitivity (0.821 and 0.821, respectively) and specificity (0.929 and 0.964, respectively). Importantly, the combination of miR-339-5p and miR-21 markedly improved AUC (0.963), sensitivity (0.929) and specificity (0.929). Conclusion Plasma miR-339-5p or miR-21 could serve as a potential biomarker for diagnosis of LA, however, the combination of miR-339-5p and miR-21 was more efficient for LA detection. [ABSTRACT FROM AUTHOR]

Lung cancer is a leading cause of cancer-related mortality, and non-small-cell lung carcinoma is responsible for almost 80% of lung cancer-related deaths. In recent years, lung cancer has shown increasing incidence but poor prognosis, and many studies have demonstrated that microRNAs play crucial roles in the development of lung carcinoma and chemoresistance. This study investigated the role of miR-339-5p involvement in lung carcinoma cell lines and chemoresistance to Taxol. We observed that miR-339-5p was significantly downregulated in Taxol-A549 cells compared with A549 cells. In vitro studies further indicated that miR-339-5p could promote colony formation and attenuate apoptosis of lung carcinoma cell lines through targeting α1,2-fucosyltransferase 1 and regulation of the downstream protein Lewis y. Furthermore, miR-339-5p was found to enhance the proliferation inhibition ability of Taxol in lung carcinoma cell lines as well as in the Taxol-A549 subclone. An in vivo study indicated that both miR-339-5p and Taxol could attenuate the growth of lung carcinoma; moreover, miR-339-5p could synergistically promote this inhibitory function of Taxol. In summary, our results suggest a miR-339-5p molecular network that is involved in controlling lung carcinoma progression. © 2017 The Authors IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 69(11):841-849, 2017 [ABSTRACT FROM AUTHOR]

This study aimed to explore the role of miR-339-5p in ovarian cancer. The expression of miR-339-5p in seven ovarian cancer cell lines (Hey, SKOV3, OVCAR5, SKOV3-IP, A2780, CAOV3, and OVCA433) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The miR-339-5p mimic and inhibitor were used to regulate its expression. Migration, invasion, and proliferation were examined. A bioinformatics analysis was used to predict targets, and a dual-luciferase reporter system was applied for validation, along with Western blot verification. Additionally, the association of miR-339-5p and its target genes with ovarian cancer was analyzed based on The Cancer Genome Atlas (TCGA) database. OVCAR5 and SKOV3 had the highest and lowest miR-339-5p expression, respectively. Inhibition of miR-339-5p expression increased the migration and invasion of OVCAR5 cells, while in SKOV3 cells, upregulated miR-339-5p attenuated the migration and invasion ability. Modulation of miR-339-5p had no effect on proliferation. The genes nucleus accumbens associated 1(BEN and BTB (POZ) domain containing) (NACC1) and B cell lymphoma-6 (bcl6) were validated to be targets of miR-339-5p. Clinically, patients with a high expression of NACC1 had a high risk in the survival analysis. miR-339-5p inhibits migration and invasion in ovarian cancer by targeting NACC1 and BCL6. miR-339-5p may be a biomarker of metastasis in ovarian cancer; NACC1 had a predictive value for ovarian cancer progression. [ABSTRACT FROM AUTHOR]

Alcohol-induced neuroinflammation is mediated by the innate immunesystem. Pro-inflammatory responses to alcohol are modulated by miRNAs. The miRNA miR-339-5p has previously been found to be upregulated in alcohol-induced neuroinflammation. However, little has been elucidated on the regulatory functions of this miRNA in alcohol-induced neuroinflammation. We investigated the function of miR-339-5p in alcohol exposed brain tissue and isolated microglial cells using ex vivo and in vitro techniques. Our results show that alcohol induces transcription of miR 339-5p, IL-6, IL-1β and TNF-α in mouse brain tissue and isolated microglial cells by activating NF-κB. Alcohol activation of NF-κB allows for nuclear translocation of the NF-κB subunit p65 and expression of pro-inflammatory mediators. miR-339-5p inhibited expression of these pro-inflammatory factors through the NF-κB pathway by abolishing IKK-β and IKK-ε activity. [ABSTRACT FROM AUTHOR]

Recent studies validate that circular RNAs have played critical regulatory functions in cancer biology. However, their contribution to prostate cancer (PCa) remained largely unclear. Our study aimed to explore the regulatory function and underlying mechanisms of circ_0086722 in PCa. The circ_0086722 levels in PCa tissues and cell lines were detected through qRT-PCR. In vivo and in vitro experiments were performed to evaluate the functions of circ_0086722 in PCa. Subsequently, the underlying mechanisms of circ_0086722 were explored with qRT-PCR, RNA immunoprecipitation, miRNA pull-down, and luciferase reporter assay experiments. Results revealed that circ_0086722 was highly expressed in PCa tissues and cell lines. Furthermore, high levels of circ_0086722 were positively correlated with pT3 stage, higher specimen Gleason score (>7), and worse biochemical recurrence-free survivals of PCa patients. Then, functional experiments revealed that circ_0086722 accelerated PCa proliferation and progression. Moreover, we demonstrated that circ_0086722 could mechanistically relieve the repressive effects of miR-339-5p on its target STAT5A, which facilitates PCa development. In conclusion, our findings revealed that circ_0086722 drives PCa development via the miR-339-5p/STAT5A axis, and it may function as a potential prognostic biomarker or therapeutic target for PCa treatment. Further studies with large sample sizes and sufficiently long follow-up periods are necessary to confirm the predictive role of circ_0086722 for the prognosis of PCa patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the molecular mechanism of hsa&#95;circ&#95;0005221 regulating the progression of PCa through the miR-339-5p/STAT5a pathway., Methods: Localizations of hsa&#95;circ&#95;0005221 and miR-339-5p in cells were detected by nuclear-cytoplasmic isolation. MiRNA-339-5p was selected as the target miRNA bound to hsa&#95;circ&#95;0005221 by RNA pull-down assay. The binding site of the luciferase reporter gene was predicted by software and the binding capability of miR-339-5p validated by luciferase assay. The expression of hsa&#95;circ&#95;0005221 in the prostatic epithelial and PCa cells was determined by qPCR. The hsa&#95;circ&#95;0005221-overexpressed plasmid and siRNA were transfected into the PCa cells for measurement of their proliferation, invasion and migration abilities and the levels of epithelial-mesenchymal transformation (EMT) and apoptosis. After knockdown of hsa&#95;circ&#95;0005221 and transfection of miR-339-5p mimics and miR-339-5p inhibitor, the proliferation, invasion and migration abilities of the DU145 and LNCaP cells were detected, and so were the levels of the EMT signature protein, STAT5a and cell apoptosis., Results: The expression of hsa&#95;circ&#95;0005221 was significantly higher in the PCa than in the prostatic epithelial cells. Nuclear-cytoplasmic isolation experiments showed that hsa&#95;circ&#95;0005221 and miR-339-5p were mainly located in the cytoplasm. The proliferation, invasion and migration abilities and EMT were decreased and the apoptosis increased in the DU145 and LNCaP cells with knockdown of hsa&#95;circ&#95;0005221, which was just the reverse in those with overexpressed hsa&#95;circ&#95;0005221. Among the top 5 miRNAs predicted by software, miR-339-5p, miR-17 and miR-520h were shown by pull-down assay to be bound to hsa&#95;circ&#95;0005221, with most obvious changes in miR-339-5p when hsa&#95;circ&#95;0005221 knocked down or overexpressed. Luciferase reporter gene assay showed the binding of hsa&#95;circ&#95;0005221 to miR-339-5p. Knockdown of hsa&#95;circ&#95;0005221 and transfection of miR-339-5p mimics into the DU145 and LNCaP cells significantly reduced the proliferation, invasion and migration abilities of the cells and the N-cad level, increased their apoptosis and E-cad level, and up-regulated the expression of STAT5a, while overexpression of hsa&#95;circ&#95;0005221 and transfection of miR-339-5p mimics induced just the opposite effects., Conclusions: Hsa&#95;circ&#95;0005221 enhances the progression of prostate cancer through the miR-339-5p/STAT5a pathway.

Colon cancer is an aggressive malignancy with very limited therapeutic approaches. The available therapeutic agents for colon cancer show strong adverse effects and poor effectiveness, indicating the urgent need to identify new therapeutic drugs for this malignancy. Kaempferol, a flavonoid found in a variety of natural foods, exhibits significant inhibitory effects on colon cancer. Here, it was found that kaempferol inhibited the proliferation of human colon cancer cells HCT116 and DLD1 in a dose-dependent manner, and the IC 50 values were 63.0 ± 12.9 and 98.3 ± 15.9 μM, respectively. Also, kaempferol treatment delayed G1 phase progression of cell cycle and induced apoptosis. Aerobic glycolysis is the major energy source for various tumor growths, including colon cancer. Indeed, kaempferol treatment impaired glucose consumption, which subsequently led to reduced lactic acid accumulation and ATP production. Mechanistically, kaempferol promoted the expression of miR-339-5p. Further studies identified hnRNPA1 and PTBP1 as two direct targets of miR-339-5p. By directly targeting hnRNPA1 and PTBP1, miR-339-5p reduced the expression of M2-type pyruvate kinase (PKM2) but induced that of PKM1. In conclusion, these data demonstrate that by modulating miR-339-5p-hnRNPA1/PTBP1-PKM2 axis, kaempferol inhibits glycolysis and colon cancer growth, which reveals a new explanation for the molecular mechanism underlying kaempferol anti-tumor.

Background: Oxidative stress has emerged as an essential factor in the pathogenesis of intestinal ischemia/reperfusion (I/R) injury. The adaptor protein p66Shc is a key regulator of reactive oxygen species (ROS) generation and a mediator of I/R damage in the intestine, but the upstream mechanisms that directly regulate p66Shc expression during intestinal I/R remain largely unknown. Recent studies have suggested that noncoding RNAs, such as circular RNAs (circRNAs), are important players in physiological and pathological processes based on their versatile regulatory roles in gene expression. The aim of this study was to elucidate the contribution of p66Shc to oxidative damage in intestinal I/R and to investigate the regulation of p66Shc by circRNA sponges. Methods: Intestinal I/R was induced in mice via superior mesenteric artery (SMA) occlusion. A miR-339-5p agomir or circ-protein kinase C beta (PRKCB) siRNA was injected intravenously before I/R challenge. In addition, Caco-2 cells were subjected to hypoxia/reoxygenation (H/R) in vitro to simulate an in vivo I/R model. Results: In vitro ) levels, suppressing NADPH oxidase activity and enhancing antioxidant enzyme expression. Moreover, miR-339-5p was identified to directly regulate p66Shc expression in the intestine. Furthermore, we found that a circRNA transcribed from the PRKCB gene, named circ-PRKCB, acted as an endogenous miR-339-5p sponge to regulate p66Shc expression. circ-PRKCB silencing or miR-339-5p overexpression significantly downregulated p66Shc expression and attenuated oxidative stress levels and I/R injury 2 - . Notably, the increased circ-PRKCB levels and decreased miR-339-5p levels associated with murine intestinal I/R were consistent with those in patients with intestinal infarction. in vivo Our findings reveal a crucial role for the circ-PRKCB/miR-339-5p/p66Shc signaling pathway in regulating oxidative stress in the I/R intestine. This pathway may be a potential therapeutic target for intestinal I/R injury.in vitro . Notably, the increased circ-PRKCB levels and decreased miR-339-5p levels associated with murine intestinal I/R were consistent with those in patients with intestinal infarction. Conclusions: Our findings reveal a crucial role for the circ-PRKCB/miR-339-5p/p66Shc signaling pathway in regulating oxidative stress in the I/R intestine. This pathway may be a potential therapeutic target for intestinal I/R injury., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Aim: The role of circRNAs in esophageal squamous cell cancer (ESCC) remains unclear. Materials & methods: Here we profiled six pair plasma circRNA in ESCC based on RNA sequencing, and then verified the elevation of hsa&#95;circ&#95;0004771 in 20 cancer tissues and 105 pair case-control plasma samples by quantitative reverse transcriptase PCR. Results: The upregulation of hsa&#95;circ&#95;0004771 was correlated with heavier tumor burden and poor prognosis, knockdown of it inhibited the ESCC cells proliferation both in vitro and in vivo . Mechanistically, hsa&#95;circ&#95;0004771 positively regulated CDC25A by acting as a molecular sponge of miR-339-5p and rescue assay confirmed this regulatory relationship. Conclusion: These results suggested that hsa&#95;circ&#95;0004771 can serve as a general less-invasive biomarker and may provide diagnostic and prognostic value in carcinoma.

This study aimed to explore the role of miR-339-5p in ovarian cancer. The expression of miR-339-5p in seven ovarian cancer cell lines (Hey, SKOV3, OVCAR5, SKOV3-IP, A2780, CAOV3, and OVCA433) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The miR-339-5p mimic and inhibitor were used to regulate its expression. Migration, invasion, and proliferation were examined. A bioinformatics analysis was used to predict targets, and a dual-luciferase reporter system was applied for validation, along with Western blot verification. Additionally, the association of miR-339-5p and its target genes with ovarian cancer was analyzed based on The Cancer Genome Atlas (TCGA) database. OVCAR5 and SKOV3 had the highest and lowest miR-339-5p expression, respectively. Inhibition of miR-339-5p expression increased the migration and invasion of OVCAR5 cells, while in SKOV3 cells, upregulated miR-339-5p attenuated the migration and invasion ability. Modulation of miR-339-5p had no effect on proliferation. The genes nucleus accumbens associated 1(BEN and BTB (POZ) domain containing) (NACC1) and B cell lymphoma-6 (bcl6) were validated to be targets of miR-339-5p. Clinically, patients with a high expression of NACC1 had a high risk in the survival analysis. miR-339-5p inhibits migration and invasion in ovarian cancer by targeting NACC1 and BCL6. miR-339-5p may be a biomarker of metastasis in ovarian cancer; NACC1 had a predictive value for ovarian cancer progression.