ALKBH5 involves in osteosarcoma tumor progression by mediating Notch signaling

Abstract

Abstract ALKBH5 is the major demethylase of ribonuclease m6A and exerts these multiple biological functions in cancer. In this study, we mainly explore the use of ALKBH5 in the development and progression of osteosarcoma and elucidate the potential molecular mechanisms by which it functions. Relative to human osteoblast cell lines (NHOst), we detected ALKBH5 expression in osteosarcoma cell lines (HOS, U2OS, and MG‐63) by RT‐PCR and western blot. By overexpression and knockout of ALKBH5 gene, to observe the effect of ALKBH5 on apoptosis, invasion and epithelial‐mesenchymal transition (EMT) of osteosarcoma cells, as well as the effect of Notch signaling pathway. We found that ALKBH5 was significantly higher in osteosarcoma cell lines than in osteoblastic cell lines. In addition, ALKBH5 overexpression promoted the proliferation, migration, and invasion of osteosarcoma cells, and simultaneously activated Notch signaling pathway and up‐regulated E‐cadherin protein. Knockout of ALKBH5 inhibited these effects in osteosarcoma cells. It was also found that up‐regulation of ALKBH5 could promote the proliferation of osteosarcoma cells in vitro and in vivo. ALKBH5 can be involved in osteosarcoma development through Notch signaling pathway regulation. ALKBH5 is therefore expected to be a new target in the treatment of osteosarcoma.

Keywords

• ALKBH5
• apoptosis
• invasion
• migration
• Notch signaling
• osteosarcoma