Experimental study on down-regulation of long non-coding RNA KCNQ1 opposite strand transcript 1 expression for reversing cisplatin resistance in human osteosarcoma cells

Abstract

Objective To investigate the role and possible mechanism of long non-coding RNA KCNQ1 opposite strand transcript 1 (KCNQ1OT1) in the development of cisplatin (DDP) resistance in osteosarcoma (OS). Methods The expression of KCNQ1OT1 in parental cells and drug-resistant cells was detected by real-time polymerase chain reaction (qPCR). The small interfering RNA (siRNA) targeting lncRNA-KCNQ1OT1 was synthetized and transfected into osteosarcoma cells. The cisplatin sensitivity half maximal inhibitory concentration (IC50), migration and invasion of OS cells were assessed with WST-1 assays and Transwell assays, respectively. The expression of epithelial-mesenchymal transition (EMT) associated molecules was detected by qPCR. Results The IC50 values of cisplatin-resistant MG63/DDP and 143B/DDP in osteosarcoma were (17.960±0.153) μmol/L and (7.725±0.183) μmol/L, respectively, which were significantly higher than the IC50 value of the parental cells [(5.074±0.159), (2.633±0.219) μmol/L] (t=101.148, 30.903, P<0.01). The relative expression levels of KCNQ1OT1 in MG63/DDP and 143B/DDP cells were 6.830±0.105 and 6.284±0.465, respectively, compared with parental cells (3.081±0.167, 2.014±0.216), the difference was statistically significant (t=22.917, 11.722, P<0.01). Knocking down the expression of KCNQ1OT1 can inhibit the migration and invasion of osteosarcoma DDP-resistant cells. After down-regulation of KCNQ1OT1, IC50 values of MG63/DDP and 143B/DDP were decreasedsignificantly. The expression of E-cadherin was down-regulated in the drug-resistant cells, and the expression of N-cadherin and Vimentin was up-regulated. After interference with KCNQ1OT1, the expression of E-cadherin was up-regulated and the expression of N-cadherin, Vimentin and Slug was down-regulated. Conclusion KCNQ1OT1 may promote osteosarcoma cisplatin resistance by regulating EMT. KCNQ1OT1 may be a potential therapeutic target for DDP-resistant osteosarcoma Key words: Long non-coding RNA; KCNQ1 opposite strand transcript 1; Osteosarcoma