miR-363 inhibits the growth, migration and invasion of hepatocellular carcinoma cells by regulating E2F3.

A growing body of evidence suggests that microRNA-363 (miR-363) plays crucial roles in tumor progression, development and metastasis, and confer resistance to chemotherapeutic drugs in several types of cancers. However, the biological function and underlying molecular mechanism of miR-363 in hepatocellular carcinoma (HCC) have not been fully elucidated. In the present study, we investigated the biological function and mechanism of miR-363 in the regulation of HCC progression. We found that miR-363 was downregulated in HCC cell lines and tissues, and a low expression level of miR-363 was associated with tumor differentiation, TNM stage and lymph node metastasis. Forced overexpression of miR-363 significantly suppressed HCC cell proliferation, migration, invasion and decreased epithelial‑mesenchymal transition (EMT) in vitro, as well as inhibited tumor growth in vivo. Analysis of the underlying mechanisms revealed that miR-363 regulated E2F transcription factor 3 (E2F3) expression by directly targeting its 3' untranslated region. E2F3 overexpression partially attenuated the tumor-suppressive effects of miR-363 in HCC cells. In addition, E2F3 expression was upregulated in the HCC tissues, and was negatively correlated with the level of miR-363 in human HCC tissues. Taken together, these results revealed that miR-363 is involved in HCC growth and invasion and functions as a tumor suppressor by negatively regulating E2F3.