Role of microRNA-141-3p in the progression and metastasis of hepatocellular carcinoma cell.

Hepatocellular carcinoma (HCC) is a leading cause of cancer related death worldwide. However, the mechanisms underlying HCC progression and metastasis are still in obscure. Here, we used bioinformatic analysis to identify miRNAs that regulate GP73, a specific marker for HCC diagnosis and prognosis. The correlations between miR-141-3p and clinic-pathological factors were analyzed in HCC patient samples; proliferation, migration, invasion, and colony formation were studied using established HCC cell lines. Expression levels of target genes (miR-141-3p, GP73, E-cadherin, N-cadherin, occludin, vimentin, and cytokeratin 18) were detected by either Western blot or qRT-PCR analysis. Xenograft models were established to evaluate tumor growth and metastasis. MiR-141-3p was significantly reduced in HCC tumors and cell lines, highly correlated with tumor progression. In contrast, GP73 was negatively correlated with miR-141-3p in HCC tumors. MiR-141-3p overexpression significantly decreased HCC cell proliferation, migration, and invasion by inhibiting epithelial-mesenchymal transition (EMT). GP73 overexpression partially restored the inhibitory effects of miR-141-3p, while miR-141-3p overexpression markedly inhibited tumor growth and pulmonary metastasis, which were partially reversed by GP73 overexpression. Our findings suggest that miR-141-3p targets GP73 to reverse EMT, subsequently inhibiting HCC progression and metastasis. Thus, overexpression of miR-141-3p could serve as a therapeutic strategy to arrest HCC.

Hou X ，Yang L ，Jiang X ，Liu Z ，Li X ，Xie S ，Li G ，Liu J ... -  《-》

Identification of invasion-metastasis-associated microRNAs in hepatocellular carcinoma based on bioinformatic analysis and experimental validation.

Lou W ，Chen J ，Ding B ，Chen D ，Zheng H ，Jiang D ，Xu L ，Bao C ，Cao G ，Fan W ... -  《Journal of Translational Medicine》

Upregulation of microRNA-140-3p inhibits epithelial-mesenchymal transition, invasion, and metastasis of hepatocellular carcinoma through inactivation of the MAPK signaling pathway by targeting GRN.

Invasion and metastasis in hepatocellular carcinoma (HCC) results in poor prognosis. Human intervention in these pathological processes may benefit the treatment of HCC. The aim of the present study is to elucidate the mechanism of miR-140-3p affecting epithelial-mesenchymal transition (EMT), invasion, and metastasis in HCC. Microarray analysis was performed for differentially expressed genes screening. The target relationship between miR-140-3p and GRN was analyzed. Small interfering RNA (siRNA) against granulin (GRN) was synthesized. EMT markers were detected, and invasion and migration were evaluated in HCC cells introduced with a miR-140-3p inhibitor or mimic, or siRNA against GRN. A mechanistic investigation was conducted for the determination of mitogen-activated protein kinase (MAPK) signaling pathway-related genes and EMT markers (E-cadherin, N-cadherin, and Vimentin). GRN was highlighted as an upregulated gene in HCC. GRN was a target gene of miR-140-3p. Elevation of miR-140-3p or inhibition of GRN restrained the EMT process and suppressed the HCC cell migration and invasion. HCC cells treated with the miR-140-3p mimic or siRNA-GRN exhibited decreased GRN expression and downregulated the expressions of the MAPK signaling pathway-related genes, N-cadherin, and Vimentin but upregulated the expression of E-cadherin. GRN silencing can reverse the activation of the MAPK signaling pathway and induction of EMT mediated by miR-140-3p inhibition. Taken together, the results show that miR-140-3p confers suppression of the MAPK signaling pathway by targeting GRN, thus inhibiting EMT, invasion, and metastasis in HCC.

Zhang QY ，Men CJ ，Ding XW 《-》

MiR-542-3p inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting UBE3C.

Accumulating evidence demonstrates that aberrant miRNAs contribute to hepatocellular carcinoma (HCC) development and progression. However, the roles of various miRNAs in HCC remain to be determined. In present research, we confirmed that a reduced miR-542-3p expression was present in HCC tissues and cell lines. Our clinical analysis revealed that the down-regulated miR-542-3p expression was significantly correlated with poor prognostic features including advanced TNM stage and venous infiltration. Moreover, we confirmed that miR-542-3p was a novel independent prognostic marker for predicting 5-year survival of HCC patients. The ectopic overexpression of miR-542-3p inhibited cell migration, invasion and EMT progress, while down-regulated miR-542-3p reversed the effect. In addition, miR-542-3p could regulate UBE3C by directly binding to its 3'-UTR. In clinical samples of HCC, miR-542-3p inversely correlated with UBE3C, which was upregulated in HCC. Alternation of UBE3C expression at least partially abolished the migration, invasion and EMT progress effects of miR-542-3p on HCC cells. In conclusion, our results indicated that miR-542-3p functioned as a tumor suppressor gene in regulating the EMT and metastasis of HCC via targeting UBE3C, and may represent a novel potential therapeutic target and prognostic marker for HCC.

Tao J ，Liu Z ，Wang Y ，Wang L ，Yao B ，Li Q ，Wang C ，Tu K ，Liu Q ... -  《-》

MicroRNA-655-3p functions as a tumor suppressor by regulating ADAM10 and β-catenin pathway in Hepatocellular Carcinoma.

Wu G ，Zheng K ，Xia S ，Wang Y ，Meng X ，Qin X ，Cheng Y ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》