Objective: Tongue cancer is a common malignant tumor in the oral and maxillofacial region, most of which is squamous cell carcinoma. Cisplatin (DDP) is one of the chemotherapy drugs for patients with tongue squamous cell carcinoma (TSCC). However, DDP resistance has become a major obstacle to its clinical application. Our study aimed to investigate the effects of long non-coding RNA (lncRNA) KCNQ1 overlapping transcript 1 (KCNQ1OT1) on DDP resistance of tongue cancer and the underlying mechanism.
Patients and methods: The levels of KCNQ1OT1, miR-124-3p, and tripartite motif containing 14 (TRIM14) were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The maximum size of tumor (MTS) assay was used to detect the cell survival rates. Furthermore, the cell proliferation was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Transwell assay was performed to detect the cell migration and invasion. Western blot assay was used to detect the protein levels of Vimentin, N-cadherin, E-cadherin, and TRIM14. The functional targets of KCNQ1OT1 and miR-124-3p, miR-124-3p and TRIM14 were predicted by starBase 3.0 and TargetScan. The relationship between KCNQ1OT1 and miR-124-3p was confirmed by Dual-Luciferase reporter assay, RNA immunoprecipitation (RIP) and RNA pull-down. Further, the relationship between miR-124-3p and TRIM14 was verified by Dual-Luciferase reporter assay. Animal experiment revealed the effect of KCNQ1OT1 on DDP resistance of tongue cancer cells in vivo.
Results: KCNQ1OT1 was upregulated in DDP-resistant tongue cancer tissues and cells, and mainly expressed in cytoplasm. Functionally, the knockdown of KCNQ1OT1 inhibited the survival rate, proliferation, migration, invasion, and EMT of the DDP-resistant tongue cancer cells. Of note, miR-124-3p acted as a target of KCNQ1OT1 and KCNQ1OT1 could reduce the expression of miR-124-3p. Moreover, miR-124-3p targeted TRIM14 and the downregulation of TRIM14 reduced the DDP resistance of tongue cancer cells. Importantly, KCNQ1OT1 regulated the TRIM14 expression by targeting miR-124-3p. Furthermore, KCNQ1OT1 knockdown reduced the DDP-resistant tumor growth and weight through the miR-124-3p/TRIM14 axis in vivo.
Conclusions: LncRNA KCNQ1OT1 promotes the DDP resistance of tongue cancer by sponging miR-124-3p to regulate TRIM14 expression.