MicroRNA-155 promotes tumor growth of human hepatocellular carcinoma by targeting ARID2

Aberrant expression of microRNA-155 (miR-155) has been reported in several human cancers and is associated with prognosis of patients. However, the clinical significance of miR-155 and its underlying mechanisms involved in hepatocarcinogenesis remain to be determined. In this study, we demonstrated that the expression of miR-155 was elevated in both hepatocellular carcinoma (HCC) tissues and cell lines. Clinical association analysis revealed that high expression of miR-155 was correlated with malignant clinicopathological characteristics including large tumor size, high Edmondson-Steiner grading and TNM tumor stage. Furthermore, its high expression conferred a reduced 5-year overall survival and disease-free survival of HCC patients. Gain- and loss-of function studies revealed that miR-155 promoted cell cycle progression, cell proliferation and inhibited apoptosis. Mechanistically, we identified AT-rich interactive domain 2 (ARID2) as a direct downstream target and functional mediator of miR-155 in HCC cells. Notably, alterations of ARID2 expression abrogated the effects of miR-155 on HCC cell proliferation, cell cycle and apoptosis. Moreover, we demonstrated that Akt phosphorylation is essential for the functional roles of miR-155 through altering Cyclin D1 and p27, which were key components of cell cycle machinery. Finally, we disclosed that the downregulation of miR-155 suppressed tumor growth of HCC by inhibiting Akt signaling pathway. In conclusion, our results indicate that miR-155 promotes tumor growth of HCC by targeting ARID2-mediated Akt phosphorylation pathway, and potentially serves as a novel prognostic biomarker and therapeutic target for HCC.