miRNA-448 inhibits cell growth by targeting BCL-2 in hepatocellular carcinoma.

Increasing evidence indicates that aberrant micro (mi)RNA-448 expression plays a critical role in the progression of several human cancers. However, the function of miRNA-448 in hepatocellular carcinoma (HCC) has not been fully investigated. miRNA-448 expression levels in HCC tissues, adjacent non-cancerous tissues (ANTs), and HCC cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR). HCC cells were treated with a miRNA-448 mimic or inhibitor, followed by cell viability measurements with the CCK-8 assay. Venn diagram analysis predicted, and dual luciferase reporter assays verified, the target gene of miRNA-448. Expression of the target gene was detected by qRT-PCR and immunohistochemistry. Growth of miRNA-448- or target gene-expressing HCC xenograft tumors in nude mice was measured. miRNA-448 was expressed at a lower level in HCC tissues than ANTs, and correlated with a larger tumor size, incomplete tumor encapsulation, and advanced Barcelona Clinic Liver Cancer stage. miRNA-448 inhibited HCC cell growth. The downstream target of miRNA-448 was BCL-2, which was highly expressed in HCC tissues and its mRNA level was negatively correlated with miRNA-448 expression. In vivo, BCL-2 attenuated the tumor inhibiting effect of miRNA-448. miRNA-448 functions as a tumor suppressor by targeting BCL-2 in HCC.

Liao ZB ，Tan XL ，Dong KS ，Zhang HW ，Chen XP ，Chu L ，Zhang BX ... -  《-》

MiR-199a-5p suppresses tumorigenesis by targeting clathrin heavy chain in hepatocellular carcinoma.

The deregulation of microRNA (miRNA) is frequently associated with a variety of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the expression and possible role of miR-199a-5p in HCC. The expression of miR-199a-5p was measured by quantitative RT-PCR in HCC. The effect of miR-199a-5p was evaluated by cell viability and colony formation assays in HCC cell lines and tumor cell growth assay in xenograft nude mice. Quantitative real time PCR results showed that miR-199a-5p was down-regulated in 77.9 % (67/86) of HCC tissues compared with adjacent nontumor tissues. MiR-199a-5p mimic reduced cell viability and colony formation by induction of cell arrest in HCC cell lines and inhibited tumor cell growth in xenograft nude mice, but miR-199a-5p inhibitor increased cell viability and colony formation in HCC cell lines and tumor cell growth in xenograft nude mice. Furthermore, CLTC was defined as a potential direct target of miR-199a-5p by MiRanda and TargetScan predictions. The dual-luciferase reporter gene assay results showed that CLTC was a direct target of miR-199a-5p. The use of miR-199a-5p mimic or inhibitor could decrease or increase CLTC protein levels in HCC cell lines. We conclude that the frequently down-regulated miR-199a-5p can regulate CLTC and might function as a tumor suppressor in HCC. Therefore, miR-199a-5p may serve as a useful therapeutic agent for miRNA-based HCC therapy.

Huang GH ，Shan H ，Li D ，Zhou B ，Pang PF ... -  《-》

MicroRNA-424-5p acts as a potential biomarker and inhibits proliferation and invasion in hepatocellular carcinoma by targeting TRIM29.

miRNA-424-5p (miR-424-5p) has been implicated in the development and progression of various tumors. However, the functional mechanisms of miR-424-5p in hepatocellular carcinoma (HCC) are unclear. In this study, we investigated the specific biological functions of miRNA in HCC. The expression of miR-424-5p was measured by qRT-PCR in HCC tissues and cell lines. Western blot and immunohistochemistry were used to detect the protein expression level of TRIM29. The relationship between miR-424-5p and the clinicopathological features of HCC patients was analyzed. Cell function experiments were performed to examine proliferation and invasion in HCC cells. The miRNA database was used to predict downstream target genes of miR-424-5p, which were verified by a luciferase reporter assay. Furthermore, cell and animal experiments confirmed that miR-424-5p exerts its biological function through the target gene TRIM29. miR-424-5p expression was decreased in HCC tissues and cell lines, and correlated with AFP, TNM stage, intrahepatic metastasis and poor overall survival in HCC. The upregulation of miR-424-5p inhibited cell proliferation and invasion in vitro and suppressed HCC tumor growth in vivo. TRIM29 was confirmed to be the downstream target gene of miR-424-5p. Finally, rescue experiments suggested that the upregulation of TRIM29 could rescue inhibitory effect of miR-424-5p overexpression on cell proliferation and migration. miR-424-5p is a tumor suppressor miRNA that inhibits cell proliferation and invasion via directly modulating TRIM29, which is related to cell proliferation and invasion in HCC. Thus, miR-424-5p may be a potential therapeutic and new prognostic marker for HCC.

Du H ，Xu Q ，Xiao S ，Wu Z ，Gong J ，Liu C ，Ren G ，Wu H ... -  《-》

BCL2L10 inhibits growth and metastasis of hepatocellular carcinoma both in vitro and in vivo.

BCL2L10 is an apoptosis-related member of the BCL-2 protein family. The role of BCL2L10 in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. This study was aimed to investigate the function and underlying mechanisms of BCL2L10 in HCC. BCL2L10 expression in human HCC and corresponding adjacent normal tissues was investigated by quantitative real-time PCR and Western blot. The biological functions of BCL2L10 in HCC cell lines were determined by cell viability, colony formation, cell apoptosis, cell cycle, and cell metastasis assays, and in vivo by tumorigenicity and lung metastasis assays in nude mice. Human cancer pathway PCR array was employed to explore the genes regulated by BCL2L10 in HCC. BCL2L10 was down-regulated in human HCC tissues compared to their adjacent non-tumor tissues. Ectopic expression of BCL2L10 in HepG2 and Huh7 cells suppressed cell growth as evidenced by cell viability and colony formation assay, and induced cell apoptosis. HCC cells transfected with BCL2L10 revealed an increased cell proportion arrested at G2/M phase, concomitant with a reduction in the cell proportion in S-phase as compared with control cells. Additional, BCL2L10 repressed cell migration and angiogenesis. Over-expression of BCL2L10 also restrained the tumorigenecity and lung metastasis capacity in nude mice. The activation of JAK-STAT3 signaling was suppressed by BCL2L10 in HCC. BCL2L10 was down-regulated in human HCC tissues compared to adjacent normal tissues. BCL2L10 suppressed HCC progression through inhibiting cell growth and metastasis. Thus, BCL2L10 functions as a tumor-suppressor in HCC. © 2016 Wiley Periodicals, Inc.

Bai Y ，Wang J ，Han J ，Xie XL ，Ji CG ，Yin J ，Chen L ，Wang CK ，Jiang XY ，Qi W ，Jiang HQ ... -  《-》

miR-10b exerts oncogenic activity in human hepatocellular carcinoma cells by targeting expression of CUB and sushi multiple domains 1 (CSMD1).

Zhu Q ，Gong L ，Wang J ，Tu Q ，Yao L ，Zhang JR ，Han XJ ，Zhu SJ ，Wang SM ，Li YH ，Zhang W ... -  《-》