Home HOME Neoplasma 2020 Neoplasma Vol.67, No.3, p.519–527, 2020

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Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

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Neoplasma Vol.67, No.3, p.519–527, 2020

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

Abstract: 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 is poorly elucidated. In this study, 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. At 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 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 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 KLF8-miR-429-SOX2 signaling pathway may provide an effective therapeutic approach to suppress the initiation and progression of OS.

Keywords: Krüppel-like factor 8; osteosarcoma; cancer stem cell-like cells; miR-429; SOX2; CD133
Published online: 02-Mar-2020
Year: 2020, Volume: 67, Issue: 3 Page From: 519, Page To: 527

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