OncomiR miR-96 and miR-182 promote cell proliferation and invasion through targeting ephrinA5 in hepatocellular carcinoma

Abstract

EphrinA5, a member of the ephrinA subclass, is downregulated in hepatocellular carcinoma (HCC) and acts as a tumor suppressor. However, the upstream regulation mechanism of ephrinA5 remains unclear. In this study, we tried to identify and characterize the roles of miR-96 and miR-182 in the regulation of ephrinA5 expression in HCC. The expression levels of miR-96 and miR-182 were examined in 47 paired HCC and para-tumoral liver tissues using quantitative real-time RT-PCR. The luciferase reporter assay and western blotting were employed to dissect the association between miR-96/182 and ephrinA5 expression. Moreover, cells were treated with synthetic miR-96/182 precursors and inhibitors to assess their effects on HCC cell growth and migration. It was found that both miR-96 and miR-182 were upregulated in HCC compared to para-tumoral normal tissues. The expression of miR-96 and miR-182 was inversely associated with ephrinA5 protein levels. Furthermore, both miR-96 and miR-182 directly targeted the 3'UTR of the ephrinA5 mRNA and suppressed protein translation. The suppression of miR-96 and miR-182 led to reduced HCC cell proliferation and migration by negatively regulating ephrinA5 expression. In conclusion, miR-96 and miR-182 may act as oncomiRs in HCC by suppressing the expression of ephrinA5 and may play important roles in hepatocarcinogenesis. © 2015 Wiley Periodicals, Inc.

Integrative proteomic and microRNA analysis of the priming phase during rat liver regeneration

“…Combining the published data with our results of IPA analysis, we speculate that miR-181c might regulate cell proliferation, apoptosis, angiogenesis and lipid metabolism in the priming phase of rat LR by targeting PAWR, KPNA4, FKBP1A and CROT through NF-κB, ERK1/2 and mTOR pathway. Previous studies showed that miR-182 could promote cell proliferation and invasion through targeting ephrinA5 and CEBPA in HCC tissues Wang et al, 2015). In our study, we found that miR-182 was up-regulated at 2 h and 6 h after PH, and the expression level of its targets ABCD1, EDEM3, TTR and DAP1 were inversely correlated with miR-182 expression.…”

miR-96 promotes cell proliferation, migration and invasion by targeting PTPN9 in breast cancer

“…The efficient overexpression of miR-96 in MCF-7 cells is shown in Supplementary Figure 2A. In support of the notion that miR-96 functions as an oncogenic miRNA214181920, the cell proliferation rate, as measured by the percentage of EdU-positive cells, was significantly increased in MCF-7 cells transfected with miR-96 mimic (Fig. 2A and C).…”

“…In agreement with this hypothesis, miR-96 has also been shown to be upregulated in various human tumor types, including colorectal cancer, hepatocellular carcinoma and chronic myeloid leukemia cells333435. It has also been reported that the suppression of miR-96 inhibited the proliferation and invasion of hepatocellular carcinoma cells203637. Although many preclinical studies show the potential of miR-96 as a therapeutic target of human cancers, few clinical studies are currently underway.…”

“…miR-96 has been shown to be overexpressed in hepatocellular carcinoma, prostate cancer, bladder cancer, lung cancer and colorectal adenocarcinoma89101112. The target genes of miR-96 include the tumor suppressor genes FOXO1 and FOXO3a in breast cancer1314, and other validated targets of miR-96 include RECK in esophageal cancer15, EphrinA5 in Hepatocellular carcinoma16, SAMD9 in non-small cell lung cancer (NSCLC)17. However, the molecular mechanism underlying the contribution of miR-96 to the development and progression of breast cancer remains poorly understood.…”

Dysregulation and functional roles of miR-183-96-182 cluster in cancer cell proliferation, invasion and metastasis

“…The PDCD4-targeted inhibition by the miR-183-96-182 cluster, described in various cancers, is summarized in Table 1. Notably, miR-96 has also been found to inhibit the TSG RECK [40, 83, 84] and EFNA5 [85]. Besides, miR-96 and miR-182 were found to have an inhibitory effect on TP53INP1 expression [62, 86].…”