miR-493-5p suppresses hepatocellular carcinoma cell proliferation through targeting GP73.

Aberrant expression of miRNAs has been documented to play critical roles in the development and progression of hepatocellular carcinoma (HCC). However, the expression pattern, functional roles and regulatory mechanism of miR-493-5p in HCC have not been addressed. Herein, we found that miR-493-5p was significantly downregulated in HCC tissues and was tightly associated with tumor size, tumor differentiation grade and TNM stage of HCC patients. Overexpression of miR-493-5p inhibited HCC cell proliferation, arrested cell cycle in G0/G1 phase and induced cell apoptosis. Bioinformatical analysis and luciferase reporter assay further proved that Golgiprotein73 (GP73), an oncogene which was generally overexpressed in HCC, acted as a novel target of miR-493-5p. MiR-493-5p could inhibit GP73 both mRNA and protein expression. Moreover, overexpression of GP73 could reverse the inhibitory effects of miR-493-5p mediated HCC cell proliferation. In addition, upregulated GP73 in HCC tissues was inversely correlated with the miR-493-5p expression levels in the HCC tissues. Collectively, our present study demonstrates that miR-493-5p is downregulated in HCC and it can suppress the proliferation of HCC cells, partly at least, via directly targeting GP73. Besides, this study provides a novel insight into the mechanism of hepatocarcinogenesis and a promising blueprint for miR-493-5p-GP73 axis-oriented treatment of HCC.

Zhao J ，Xu T ，Wang F ，Cai W ，Chen L ... -  《-》

miR-383 inhibits hepatocellular carcinoma cell proliferation via targeting APRIL.

Chen L ，Guan H ，Gu C ，Cao Y ，Shao J ，Wang F ... -  《-》

MicroRNA-548a-5p promotes proliferation and inhibits apoptosis in hepatocellular carcinoma cells by targeting Tg737.

Zhao G ，Wang T ，Huang QK ，Pu M ，Sun W ，Zhang ZC ，Ling R ，Tao KS ... -  《-》

MiR-200c-5p suppresses proliferation and metastasis of human hepatocellular carcinoma (HCC) via suppressing MAD2L1.

To explore the biological functions of miR-200c-5p/MAD2L1 axis on the proliferation and metastasis of human hepatocellular carcinoma (HCC) cells. The expression levels of miR-200c-5p and MAD2L1 in HCC tissues, adjacent tissues as well as HCC cell lines were detected by RT-qPCR or Western blot. The interaction between miR-200c-5p and MAD2L1 was verified by dual luciferase reporter gene system. Transfection was performed to manipulate the expression of miR-200c-5p and MAD2L1 in HCCLM3 cells. Colony formation, MTT, wound healing and Transwell assays were applied to measure the cell proliferation, migration and invasion of HCC, besides, flow cytometry analysis was also conducted to evaluate HCC cell cycle and apoptosis. Low expression of miR-200c-5p and remarkable overexpression of MAD2L1 was uncovered in HCC tissues and cells compared with the normal. The aberrant expression of miR-200c-5p and MAD2L1 was correlated with tumor stage, adjacent organ invasion and prognosis. Direct target relationship between miR-200c-5p and MAD2L1 was confirmed by dual luciferase reporting assay. Up-regulation of miR-200c-5p downregulated MAD2L1 and suppressed the proliferation, migration, invasion and induced apoptosis and cell cycle arrest of HCC cells. Moreover, MAD2L1 promoted HCC cell viabilities and co-transfection of MAD2L1 restored the anti-tumor effects of miR-200c-5p overexpression. Replenishing of miR-200c-5p inhibited the proliferation, migration and invasion of HCC cells by suppressing MAD2L1. MiR-200c-5p can serve as a prognostic indicator and a promising therapeutic target for HCC patients.

Li Y ，Bai W ，Zhang J 《-》

Long non-coding RNA NEAT1 promotes hepatocellular carcinoma cell proliferation through the regulation of miR-129-5p-VCP-IκB.

Long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) plays an important role in the pathogenesis and development of several types of cancer. However, the functional mechanism of NEAT1 in hepatocellular carcinoma (HCC) remains unclear. NEAT1 and microRNA (miR)-129-5p expression in HCC tissues and cell lines was quantified by means of quantitative PCR. The effects of NEAT1 expression inhibition or upregulation in HCC cell lines were analyzed in terms of cell viability and apoptosis. Biological software was used to predict the binding sites of NEAT1 and miR-129-5p. The expression of the miR-129-5p target molecules valosin-containing protein (VCP) and IκB was detected using Western blotting. The effect of NEAT1 on tumor growth was observed in mouse models of transplanted hepatoma. In the present study, it was concluded that the expression of NEAT1 was significantly increased in the HCC tissues and cell lines. Meanwhile, after downregulating NEAT1 expression in HepG2/Huh7 cell lines, the cell viability was significantly lowered, whereas the corresponding rate of apoptosis was significantly increased. Additionally, it was found that the NEAT1 and miR-129-5p expression showed a negative correlation in HCC tissues. It was further proved that there was a certain negative regulatory mechanism between NEAT1 and miR-129-5p, which was related to the expression of VCP and IκB. The mouse model experiments confirmed that the interference with NEAT1 expression inhibited tumor growth. The study concluded that the overexpression of NEAT1 inhibited the expression of miR-129-5p by regulating VCP/IκB, thereby promoting the proliferation of HCC cells. This study provides new insights into the pathogenesis of HCC, as well as identifying new target genes for diagnosis and treatment.NEW & NOTEWORTHY The results provide strong evidence that upregulated NEAT1 promotes the proliferation of cancer cells in hepatocellular carcinoma (HCC) and this regulatory mechanism depends on the microRNA (miR)-129-5p-valosin-containing protein-IκB axis. The study also indicates that NEAT1 could be a potential therapeutic target for HCC.

Fang L ，Sun J ，Pan Z ，Song Y ，Zhong L ，Zhang Y ，Liu Y ，Zheng X ，Huang P ... -  《-》