lncRNA HOXA11‐AS maintains the stemness of oral squamous cell carcinoma stem cells and reduces the radiosensitivity by targeting miR‐518a‐3p/PDK1

Abstract

AbstractObjectiveOral squamous cell carcinoma (OSCC) is the most prevailing oral malignancy. The lncRNA HOXA11‐AS shows prominent roles in OSCC. This study explored the effects of lncRNA HOXA11‐AS on regulating OSCC stem cell stemness and radiosensitivity by targeting miR‐518a‐3p/PDK1.MethodsHuman OSCC cell lines SCC9 and SCC15 were selected. CD133+ cancer stem cells (CSCs) were sorted by immunomagnetic beads. CD133 expression in cells and HOXA11‐AS expression in SCC9, SCC15, and CD133+ SCC9, CD133+ SCC15 cells were assessed by flow cytometry and RT‐qPCR. HOXA11‐AS was silenced/overexpressed in SCC9, SCC15, CD133+ SCC9, and CD133+ SCC15 cells. Cell proliferation, radiosensitivity, invasion, and stem cell sphere formation ability were examined by CCK‐8, colony formation, Transwell, and stem cell sphere formation. The levels of stemness‐related genes (Oct4, Nanog, Sox2), miR‐518a‐3p, epithelial–mesenchymal transition (EMT)‐related proteins (E‐cadherin, Vimentin, N‐cadherin), and PDK1 were assessed by RT‐qPCR and Western blot assay.ResultsHOXA11‐AS was up‐regulated in SCC9, SCC15, CD133+ SCC9, and CD133+ SCC15 cells. HOXA11‐AS silencing inhibited OSCC proliferation and invasion and enhanced radiosensitivity. HOXA11‐AS maintained CSC stemness in OSCC. HOXA11‐AS silencing reduced CD133+ SCC9 and CD133+ SCC15 stem cell sphere formation ability, reduced stem cell stemness‐related gene levels, and inhibited EMT. HOXA11‐AS regulated OSCC stem cell stemness and radiosensitivity by targeting miR‐518a‐3p. PDK1 overexpression annulled the regulatory effects of HOXA11‐AS silencing on OSCC cell stem cell stemness and radiosensitivity.ConclusionIn vitro lncRNA HOXA11‐AS silencing inhibited OSCC stem cell stemness by targeting the miR‐518a‐3p/PDK1 axis, thus enhancing OSCC cell radiosensitivity.