Exploring roles of MiR-372-3p in proliferation of hepatocellular carcinoma cells

Abstract

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. HCC has a replicative immortality and sustained proliferation rate. In addition, cell cycle-related protein regulating proliferation in cancer are often found dysregulated, allowing cancer cells to proceed their proliferation uncontrollably. Recently, a small non-coding RNA, microRNA (miRNA), was found to play an important role in numerous biological functions. Specific miRNA may ameliorate or promote cancer progression through different target mRNA. MiR-372-3p has been explored in various cancers such as colon cancer, colorectal cancer, and glioma. However, its functions have been rarely studied in HCC, especially in the aspect of cancer proliferation. This study, thus, aims to investigate its role in HCC cell line proliferation by introducing miR-372-3p overexpression vector into these cell lines. Results indicated that normal hepatocyte exhibited higher expression of miR-372-3p compared to that of HCC cells. Decelerated proliferation rate was detected in miR-372-3p overexpressing HCC cells. BrdU incorporation assay also indicated that miR-372-3p expression in HCC cells interfere the transition from G1 to S phase. G1-S phase cell cycle-related mRNA expression was different in miR-372-3p overexpressing cells compared to that of control. Dual-luciferase assay revealed that CCND1 was one of the miR-372-3p target mRNAs. Moreover, cyclin D1 protein level in miR-372-3p overexpressing cell lines was found downregulated compared to that of control. Therefore, it can be concluded that miR-372-3p interacts with CCND1 mRNA to prevent translation and to impede the cell cycle progression from G1 to S phase in HCC cell lines.