miR-15a-5p Regulates Liver Cancer Cell Migration, Apoptosis and Cell Cycle Progression by Targeting Transcription Factor E2F3
Yulong Li, Dan Li, Yang Yang, Jingjie Wang
Abstract
Liver cancer is a prevalent tumor with high incidence and mortality. MicroRNAs participate in cancer pathogenesis and miR-15a-5p may influence tumor suppression in many cancers. Herein, we analyzed the effect of miR-15a-5p in liver cancer cell migration, apoptosis, and the cell cycle. RT-PCR was performed to measure miR-15a-5p expression levels, transwell assays were applied to investigate the effect of miR-15a-5p on cell migration, and flow cytometry was performed to explore the impact of miR-15a-5p on apoptosis and the cell cycle in Hep3B and HepG2 cells. Luciferase reporter assays and Western blotting were employed to determinate the relationship between E2F3 and miR-15a-5p in liver cancer cells. Expression of E2F3 was detected by bioinformatics analysis and RT-PCR in liver cancer. Small interfering RNA (si-RNA) was used to silence E2F3 expression and assess the effect on migration, apoptosis, and the cell cycle in Hep3B/HepG2 cells. The results demonstrated that miR-15a-5p was downregulated in human liver cancer tissue, and enhancing the expression of miR-15a-5p suppressed migration in liver cancer cells, induced apoptosis, and caused G1 phase arrest. In vivo assays were further performed and miR-15a-5p inhibited the growth of liver cancer. miR-15a-5p appeared to target E2F3, and RT-PCR and bioinformatic analyses indicated that E2F3 expression was higher in liver cancer than control tissues. Silencing E2F3 expression decreased cell migration, induced apoptosis, and caused G1 phase arrest in Hep3B/HepG2 cells. These findings indicate that miR-15a-5p regulates liver cancer cell migration, apoptosis, and growth by targeting E2F3. Thus, miR-15a-5p may act as a suppressor role in liver cancer.