Vitamin D3 mediates miR-15a-5p inhibition of liver cancer cell proliferation via targeting E2F3

Vitamin D3 has been demonstrated to suppress the development and progression of liver cancer, but the mechanism is unclear. The effects of vitamin D3 and microRNA (miR)-15a-5p on liver cancer cells were investigated in the present study using MTT and colony formation assays, flow cytometry, western blotting and reverse transcription-quantitative PCR. A dual-luciferase reporter assay was performed to determine whether E2F transcription factor 3 (E2F3) was a target of miR-15a-5p. The effects of silencing the E2F3 gene expression in liver cancer cells were investigated using a small interfering RNA. Vitamin D3 suppressed liver cancer cell proliferation, induced apoptosis and increased miR-15a-5p expression. Treatment with the miR-15a-5p mimics significantly suppressed liver cancer cell proliferation compared with that of the controls. Bioinformatics analysis and a dual-luciferase reporter assay demonstrated that E2F3 was a target of miR-15a-5p and that silencing E2F3 inhibited liver cancer cell proliferation. Therefore, Vitamin D3 suppressed cell proliferation by miR-15a-5p-mediated silencing of E2F3 gene expression. These findings suggested a role for vitamin D3 and E2F3 targeting as potential novel liver cancer therapies.