miR‐376a suppresses proliferation and induces apoptosis in hepatocellular carcinoma

Zheng, Yan; Li, Yin; Chen, Huan; Yang, Shengsheng; Pan, Chuanyong; Lu, Shan; Miao, Mingyong; Jiao, Binghua

doi:10.1016/j.febslet.2012.05.054

Cited by 77 publications

(62 citation statements)

References 35 publications

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“…MicroRNA-376a (miR-376a) has been reported in several human cancers, including upregulation in esophageal cancer tissues, plasma of breast cancer, and downregulation in melanoma, and hepatocellular carcinoma (Zehavi et al, 2012;Zheng et al, 2012;Cuk et al, 2013;Zhao et al, 2013). In particular, Kunte et al found that levels of miR-376a expression were significantly increased with CRC tumor development, using the azoxymethane (AOM)-treated rat model (Kunte et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Expression and Clinical Significance of MicroRNA-376a in Colorectal Cancer

Wu²,

Li³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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The incidence of colorectal cancer (CRC) is increasing in many Asian countries and microRNAs have already been proven to be associated with tumorigenesis. Currently, microRNA-376a (miR-376a) expression and association with clinical factors in CRC remains unclear. In this study, real-time quantitative reverse transcriptasepolymerase chain reaction (qRT-PCR) was carried out on 53 matched pairs of CRC and adjacent normal mucosa to investigate the expression levels of miR-376a. According to the high or low expression of miR-376a, patients were divided into two groups. The relationship between miR-376a expression and clinicopathological factors of 53 patients was evaluated. Survival analysis of 53 CRC patients was performed with clinical followup information and survival curves were assessed by the Kaplan-Meier method. Immunohistochemistry (IHC) staining was performed on sections of paraffin-embedded tissue to investigate the vascular endothelial growth factor (VEGF) expression. MiR-376a showed low expression in cancer tissues compared to the adjacent normal tissues and altered high miR-376a expression tended to be positively correlated with advanced lymph node metastasis and shorter patient survival. VEGF IHC positivity was significantly more common in patients with high expression levels of miR-376a.Those results demonstrated that miR-376a may be a meaningful prognostic biomarker and potential therapeutic target in colorectal cancer.

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Section: Introductionmentioning

confidence: 99%

Expression and Clinical Significance of MicroRNA-376a in Colorectal Cancer

Wu²,

Li³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…It was found in our previous study [3] that miR-376a was frequently down-regulated in human HCC specimens, but the underlying mechanism remains obscure. Knowing that epigenetic alterations can deregulate Dlk1-Dio3 microRNA cluster in epithelial ovarian cancer [7], we wondered whether it was also responsible for the dysregulation of miR-376a in HCC.…”

Section: Resultsmentioning

confidence: 99%

“…Although many studies have described multiple genetic and epigenetic changes in HCC, the current evidence cannot explain the full complexity of HCC [2]. Our previous study demonstrated that miR-376a suppressed the proliferation and induced the apoptosis of HCC cells [3], but little is known about the underlying mechanism of its deregulation in HCC.…”

Section: Introductionmentioning

confidence: 99%

MiR-376a and Histone Deacetylation 9 Form A Regulatory Circuitry in Hepatocellular Carcinoma

Zheng

Chen

Yin³

et al. 2015

Cell Physiol Biochem

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Background/Aims: Our previous study has demonstrated that down-regulation of miR-376a might contribute to the development of hepatocellular carcinoma (HCC), but the mechanism underlying this down-regulation remains obscure. Methods/Results: histone deacetylase (HDAC) inhibitor increased the level of miR-376a in L02 and Huh7 cells by up-regulating the acetylation level of histone 3 at the Maternally expressed 3 (Meg3) differentially methylated region (DMR). Interestingly, HDAC9, a histone deacetylase responsible for deacetylating lysine 18 of histone 3 (H3K18), was identified as the target of miR-376a. In addition, HDAC9 siRNA increased the expression of miR-376a by up-regulating the global histone H3K18 acetylation level, with Meg3 DMR included. Finally, miR-376a and HDAC9 were inversely correlated in HCC. Conclusion: HDAC9 plays an important role both as effects and targets of miR-376a.

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“…Zheng et al reported that miR-376a was downregulated in hepatocellular carcinoma tissues and cell lines and could suppress proliferation and induce apoptosis in hepatocellular carcinoma [22]. Fellenberg et al [23].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of microRNA-376a in Gastric Cancer and Association with Poor Prognosis

Zhang¹,

Ma²,

Wu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: MicroRNAs have a significant role in the tumorigenesis and progression of cancers, including gastric cancer (GC). Our study aimed to identify a novel biomarker to predict the prognosis of patients with GC. Methods: The GC microarray dataset, GSE28700, was downloaded from the Gene Expression Omnibus (GEO) database and screened for differentially expressed miRNAs (DEMs). The downregulation of miR-376a expression was verified in GC cell lines and 82 paired GC tissues by performing RT-qPCR and the correlation between its expression and clinicopathological characteristics was also explored. The target genes of miR-376a were predicted using TargetScan7.1, miRDB, and DIANA website tools. A functional enrichment analysis was performed to explore the biological role of the common target genes. Results: Bioinformatics analysis found that miR-376a was downregulated in GC tissues. Compared with the control group, RT-qPCR results showed that the expression of miR-376a in GC cell lines and tissues were also significantly decreased. The expression of miR-376a was statistically associated with T and N stage. Survival analysis with Kaplan–Meier showed that GC patients in the low expression group had a poorer prognosis than those in the high expression group (median survival of 26.4 and 46.9 months, respectively). Univariate and multivariate analysis demonstrated that low miR-376a expression was an independent prognostic marker for poor survival. Functional enrichment analysis indicated that the common targets genes were involved in cell–cell communication, VEGF and mTOR1-mediated signaling, and epithelial-to-mesenchymal transition (EMT). Conclusion: The results suggest that miR-376a could play an important role in the tumorigenesis and progression of GC and act as a novel therapeutic target and prognostic indicator in patients with GC.

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miR‐376a suppresses proliferation and induces apoptosis in hepatocellular carcinoma

Cited by 77 publications

References 35 publications

Expression and Clinical Significance of MicroRNA-376a in Colorectal Cancer

Expression and Clinical Significance of MicroRNA-376a in Colorectal Cancer

MiR-376a and Histone Deacetylation 9 Form A Regulatory Circuitry in Hepatocellular Carcinoma

Downregulation of microRNA-376a in Gastric Cancer and Association with Poor Prognosis

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