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

Abstract

Objective: Oral 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. Methods: Human 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, epithelialmesenchymal transition (EMT)-related proteins (E-cadherin, Vimentin, N-cadherin), and PDK1 were assessed by RT-qPCR and Western blot assay. Results: HOXA11-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. Conclusion: In vitro lncRNA HOXA11-AS silencing inhibited OSCC stem cell stemness by targeting the miR-518a-3p/PDK1 axis, thus enhancing OSCC cell radiosensitivity. K E Y W O R D S cancer stem cells, lncRNA HOXA11-AS, miR-518a-3p, oral squamous cell carcinoma, radiosensitivity Baojun Li and Yuanjing Lv contributed equally to this study.

Role of long non-coding RNA in chemoradiotherapy resistance of nasopharyngeal carcinoma

“…MAGI2-AS3 can regulate the expression of target genes GDPD5 and SEC61A1 through sponge miR-2185p, thereby regulating the proliferation, migration and EMT of NPC cells, as well as the cisplatin resistance of NPC ( 22 ). HOXA11-AS is pivotal in various cancers such as lung adenocarcinoma ( 44 ), oral squamous cell carcinoma ( 45 ), gastric cancer ( 46 ), prostate cancer ( 47 ), and breast cancer ( 48 ) and is closely related to NPC. HOXA11-AS is increasingly expressed in cisplatin-resistant NPC cells and knocking down HOXA11-AS could increase the expression of miR-454-3p and inhibit the expression of target gene c-Met, thereby increasing the sensitivity of the tumor cells to cisplatin ( 23 ).…”