MicroRNA‑145‑5p inhibits osteosarcoma cell�proliferation by targeting E2F transcription factor 3

Abstract

Osteosarcoma is a common type of bone tumor that primarily occurs in children and young adults. MicroRNA (miRNA/miR) dysregulation is associated with the progression of osteosarcoma; therefore, the aim of the present study was to investigate the biological functions and molecular mechanisms of miR-145-5p in osteosarcoma. The expression of miR-145-5p in osteosarcoma tissues and cell lines was quantified using reverse transcription-quantitative PCR (RT-qPCR). The effect of miR-145-5p on the proliferation of osteosarcoma cells was detected using Cell Counting Kit-8 and colony formation assays, as well as cell cycle distribution analysis. The effect of miR-145-5p on tumor growth was further investigated in vivo using a subcutaneous tumor model in nude mice. The interaction between miR-145-5p and E2F transcription factor 3 (E2F3) was determined using bioinformatics analysis, a luciferase assay, RT-qPCR and western blotting. The results revealed that miR-145-5p expression was decreased in osteosarcoma cell lines and tissues compared with the corresponding normal controls. Increased miR-145-5p expression inhibited the proliferation and colony formation ability of osteosarcoma cells, and induced G1 phase arrest. Furthermore, mice injected with tumor cells overexpressing miR-145-5p exhibited smaller tumors than those in the control group. Further investigation revealed that miR-145-5p binds to and decreases the expression of E2F3. In addition, the mRNA levels of E2F3 were negatively associated with miR-145-5p in osteosarcoma tissues, and increasing E2F3 expression abrogated the inhibitory effects of miR-145-5p on osteosarcoma cells. Collectively, the results obtained in the present study suggest that miR-145-5p may suppress the progression of osteosarcoma, and may serve as a useful biomarker for the diagnosis of osteosarcoma, as well as a therapeutic target.