KLF8 promotes cancer stem cell-like phenotypes in osteosarcoma through miR-429-SOX2 signaling

Year, pages: 2020, 519 - 527

Krüppel-like factor 8 (KLF8) regulates critical gene transcription associated with different types of cancer. A novel paradigm in tumor biology suggests that the initiation and progression of osteosarcoma (OS) are driven by osteosarcoma stem cell-like cells (OSCs), but the role and underlying mechanisms of KLF8 in OSCs are poorly elucidated. In this study, an obviously increased level of KLF8 is shown in 9 out of 10 primary OS tissues and is associated with the poor progression-free interval. Significantly, KLF8 expression in CD133+ OSCs is higher than that in CD133- counterparts. By knocking down KLF8 in CD133+ OSCs, we show that si-KLF8-OSCs can hardly form compact spheres. In the meantime, infection with si-KLF8 in CD133+ OSCs results in the downregulation of OCT4 and SOX2; increased adriamycin (ADM) sensitivity; and decreased tumorigenic potential in vivo. Mechanisms study demonstrates that KLF8 directly binds the miR-429 promoter region and regulates its expression transcriptionally. Furthermore, we indicate that miR-429 directly targets SOX2 to mediate cancer stem cell-like features in CD133+ OSCs. In the clinic, miR-429 levels are negatively associated with KLF8 levels in OS, suggesting that an elevated KLF8/miR-429 ratio may have clinical value as a predictive biomarker. In conclusion, targeting the KLF8-miR-429-SOX2 signaling pathway may provide an effective therapeutic approach to suppress the initiation and progression of OS.

Zhang, L., Yang, P., Liu, Q., Wang, J., Yan, F., Duan, L., Lin, F. 2020. KLF8 promotes cancer stem cell-like phenotypes in osteosarcoma through miR-429-SOX2 signaling. In NEOPLASMA, vol. 67, no.3, pp. 519-527. 0028-2685. DOI: https://doi.org/10.4149/neo_2020_190711N624

Zhang, L., Yang, P., Liu, Q., Wang, J., Yan, F., Duan, L., Lin, F. (2020). KLF8 promotes cancer stem cell-like phenotypes in osteosarcoma through miR-429-SOX2 signaling. NEOPLASMA, 67(3), 519-527. 0028-2685. DOI: https://doi.org/10.4149/neo_2020_190711N624

Publisher: AEPress, Ltd.