Involvement of microRNA-224 in cell proliferation, migration, invasion, and anti-apoptosis in hepatocellular carcinoma.

Changes in microRNA (miRNA) expression have been detected in a broad range of biological processes including cancer. Here we determined the role of miRNA dysregulation in hepatocellular carcinoma (HCC). We investigated the expression of nine cancer-related miRNAs in HCC. Among these, miR-224 was the most significantly uprgulated in HCC tissues (n = 18), compared with normal (n = 9) and HCC adjacent non-tumorous liver tissues (n = 18). After leading-in currently reported gene targets from Sanger miRBase, we characterized the expression profiles of target genes of miR-224 using cDNA microarray. The altered expression was subsequently validated by real-time polymerase chain reaction and Western blot. The phenotypic changes by miR-224 expression were identified by cell viability, apoptosis, and in vitro scratch assays. The microarray analysis and miRNA target prediction analysis allowed the identification of significant changes in 68 putative gene targets after overexpression of miR-224. The high-ranking genes CDC42, CDH1, PAK2, BCL-2, and MAPK1 were confirmed as important targets of miR-224 and involvement in hepatocarcinogenesis. Overexpression of miR-224 significantly in Hek293 and Huh7 cells altered the expression levels of CDC42, CDH1, PAK2, and BCL-2 at both mRNA and protein levels. Similar changes in the expression of the same genes were also observed in HCC tissues. Via functional analyses, cell proliferation, migration and anti-apoptosis were proved to be affected by miR-224 expression. The results suggest that miR-224 plays a role in cell proliferation, migration, invasion, and anti-apoptosis in HCC by directly binding to its gene targets, implicating this RNA in HCC development and progression.

Zhang Y ，Takahashi S ，Tasaka A ，Yoshima T ，Ochi H ，Chayama K ... -  《-》

MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo.

He XX ，Chang Y ，Meng FY ，Wang MY ，Xie QH ，Tang F ，Li PY ，Song YH ，Lin JS ... -  《-》

Expression profile of microRNA-200 family in hepatocellular carcinoma with bile duct tumor thrombus.

Yeh TS ，Wang F ，Chen TC ，Yeh CN ，Yu MC ，Jan YY ，Chen MF ... -  《-》

MicroRNA-224 is upregulated in HepG2 cells and involved in cellular migration and invasion.

Li Q ，Wang G ，Shan JL ，Yang ZX ，Wang HZ ，Feng J ，Zhen JJ ，Chen C ，Zhang ZM ，Xu W ，Luo XZ ，Wang D ... -  《-》

Underexpressed microRNA-199b-5p targets hypoxia-inducible factor-1α in hepatocellular carcinoma and predicts prognosis of hepatocellular carcinoma patients.

MicroRNAs are short noncoding RNA molecules that are responsible for the posttranscriptional regulation of target genes. The aim of this study was to determine whether microRNA-199b-5p (miR-199b) plays a role in the progression and prognosis of hepatocellular carcinoma (HCC), and to elucidate whether hypoxia-inducible factor-1α (Hif1α) is regulated by miR-199b. In this study, 35 matched HCCs and cirrhosis tissues were assayed for miR-199b and Hif1α expression. To evaluate the role of miR-199b, we assessed cell proliferation rate and clonogenic survival of miR-199b- or negative control-transfected cells by MTT and clone formation assay, respectively. In addition, the regulation of Hif1α by miR-199b was evaluated by Western blotting and luciferase assay. MiR-199b was downregulated in 77% of HCCs, whereas Hif1α protein was upregulated in 69% of cases. A significant inverse correlation between miR-199b and Hif1α was observed in HCCs. Patients with lower levels of miR-199b expression had poorer overall survival and progression-free survival rates, whereas patients with higher levels of miR-199b expression had better survival. Moreover, miR-199b could restrain cell growth and obviously enhance the radiosensitizing effect of HepG2 cells. MiR-199b and pGL3-Hif1α vector-transfected cells showed suppressed Hif1α protein expression and significant reduced luciferase activity. Underexpressed miR-199b, which may be via the upregulation of Hif1α in HCCs, is inversely correlated with survival and directly correlated with the malignant status of HCC patients.

Wang C ，Song B ，Song W ，Liu J ，Sun A ，Wu D ，Yu H ，Lian J ，Chen L ，Han J ... -  《-》