BAHD1 promotes osetosarcoma recurrence by enhancing tumor cell escape from chemotherapy-induced senescence

Abstract

Abstract Objective To investigate the role and mechanism of BAHD1 in the proliferation and migration of osteosarcoma cells escaping from senescence. Methods Osteosarcoma cell lines U2OS and MG63 were cultured in vitro. Doxorubicin (DOX) and cisplatin induced U2OS and MG63 into a senescent state. The medium without DOX and CIS was replaced for continuous culture. Some cells were observed to proliferate again, which were defined as senescence-escaped OS cells (SEOS). The DOX group and CIS group were divided respectively. The DOX and CIS groups are divided into: the parent U2OS group, the U2OS SEOS cells at the 9th passage group, the parent MG63 group, and the MG63 SEOS cells at the 9th passage group. The expression of BAHD1 was detected by qRT PCR, Western blot and immunofluorescence. Cell count, CCK-8 test, agarose clone formation test, flow cytometry, etc. were used to detect cell proliferation. Cell Migration Assay was used to detect cell migration. Tumor Xenografts was used to detect the ability of cells to form tumors. The effect of BAHD1 was detected by RNA interference assay. Results The expression of BAHD1, cell cycle related proteins YWHAZ, CCND1 and stem cell factor KLF4 were significantly increased in SEOS cells at the 9th passage group compared with the parent group. Cell cycle enters S phase more quickly. After knockdown of BAHD1 expression, the above results were significantly recalled, and the ability of migration, cloning and tumor formation was significantly reduced. Conclusion The increased expression of BAHD1 is crucial in the progression of osteosarcoma, which may be achieved by up regulating the cell cycle related proteins YWHAZ, CCND1 and stem cell factor KLF4.