miR-29a suppresses the growth and metastasis of hepatocellular carcinoma through IFITM3

The interferon-induced transmembrane protein 3 (IFITM3, also called 1-8U) gene represents dysregulated expression in various tumors and is involved in tumorigenesis and progression. However, the role of IFITM3 and its underlying mechanism in hepatocellular carcinoma (HCC) are still far from elucidated. MicroRNAs (miRNAs), a class of endogenous (approximately 22 nucleotides) small noncoding RNAs, can post-transcriptionally regulate gene expression by repressing protein translation or silencing the expression of target genes that play critical roles in various cancers. miR-29a was identified as being aberrantly expressed in a significant proportion of HCC. However, the correlation between IFITM3 and miR-29a has not been reported to date. In this study, we investigated the expression of IFITM3 in HCC and its effect on the biological behavior of HCC cells as well as the association between IFITM3 and miR-29a. We determined that IFITM3 was upregulated and miR-29a downregulated in HCC tissues and that they were associated with HCC tumor size, tumor multifocal, and venous invasion. The expression of IFITM3 in HCC tissues was negatively correlated with miR-29a expression. Additionally, IFITM3 overexpression and miR-29a nonoverexpression were related to poor prognosis of HCC patients. Knockdown of IFITM3 inhibited migration, invasion, proliferation and promoted apoptosis of HCC cells, which are consistent with the effects of upregulated miR-29a. Additionally, after upregulation of IFITM3, the invasion, migration and proliferation abilities of HL-7702 cells were increased, but the apoptosis rate was decreased. Furthermore, using a Dual-Luciferase reporter gene assay, we identified IFITM3 as a new functional target gene of miR-29a. In conclusion, our findings demonstrated that the migration, invasion, proliferation and apoptosis features of HCC cells could be regulated by miR-29a via IFITM3. Thus, the present study indicated that miR-29a and IFITM3 play critical roles in the development and progression of HCC, revealing that miR-29a and IFITM3 may be novel potential therapeutic targets for patients with HCC.