MiR-371b-5p reduces osteosarcoma cell migration and proliferation to induce apoptosis by targeting FUT4

In our previous study (PMID: 34671604), we found that miR-317b-5b not only exerted anti-tumor effect, but also downregulated FUT4 expression in human myeloma cell line 143B. This study aims to investigate the biological function of miR-371b-5p in osteosarcoma progression and the role of FUT4 in this process. For in vitro investigations, the human osteosarcoma cell lines (SaOS2, 143B, KHOS and U2OS) as well as the human osteoblast cell line (hFOB1.19) were employed as models. The QRT-PCR assay was utilized to determine the relative amounts of miR-371b-5p and FUT4 expression in the cells. The functions and effects of miR-371b-5p on the abilities to proliferate, migrate, apoptosis and invade of KHOS and U2OS in osteosarcoma cells were investigated using assays including CCK-8, colony formation, EDU, wound-healing, Western blot, TUNEL and Transwell assay. The correlations between miR-371b-5p, its downstream gene FUT4 and its potential mechanisms in mediating osteosarcoma progression were explored with the assistance of dual-luciferase reporter analysis together with rescue experiments. MiR-371b-5p was less expressed in osteosarcoma cells compared with osteoblasts. Its overexpression significantly inhibited the abilities to proliferate, invade and migrate to promote apoptosis of osteosarcoma cells. The correlations between FUT4 and miR-371b-5p was established by the gene analysis of the dual-luciferase reporter analysis. FUT4 expression was dramatically decreased after the process of miR-371b-5p mimics being transfected into KHOS and U2OS cells. Additionally, overexpression of FUT4 induced osteosarcoma cell apoptosis and partially overcame miR-371b-5p's inhibitory effects on osteosarcoma cell's abilities to proliferate, invade and migrate. Osteosarcoma cells exhibit down-regulation of miR-371b-5p, that prevents osteosarcoma cells from proliferating, invading and migrating in order to promote osteosarcoma cell apoptosis through concentrating on the breakdown of FUT4.