Long noncoding RNA (lncRNA) KCNQ1OT1 (KCNQ1 opposite strand/antisense transcript 1) has been shown to participate in the tumorigenesis of several types of cancers. However, little is known about the role of KCNQ1OT1 in the chemoresistance of osteosarcoma (OS). In this study, we concentrated on the function and mechanism of KCNQ1OT1 in cisplatin resistance of OS cells. We demonstrated that KCNQ1OT1 levels were upregulated in cisplatin-resistant OS tissues and cell lines. Moreover, knockdown of KCNQ1OT1 inhibited cell proliferation, migration, and invasion and decreased cisplatin resistance in osteosarcoma 143B cells. Additionally, bioinformatics analysis and dual-luciferase reporter assays showed that miR-335-5p directly targeted KCNQ1OT1 and the 3′-UTR of β-catenin mRNA, indicating that KCNQ1OT1 regulated the expression of β-catenin via endogenous sponging of miR-335-5p. Overall, KCNQ1OT1 modulated cisplatin resistance in OS through the miR-335-5p/β-catenin axis, indicating that KCNQ1OT1 aggravates OS progression and chemoresistance to cisplatin through induction of β-catenin expression by adsorbing miR-335-5p in cisplatin-resistant OS cells, providing a theoretical basis for the treatment of chemoresistant OS.

长非编码RNA（lncRNA）KCNQ1OT1（KCNQ1相反链/反义转录物1）已显示参与多种类型癌症的肿瘤发生。然而，关于KCNQ1OT1在骨肉瘤（OS）化学耐药性中的作用了解甚少。在这项研究中，我们集中于KCNQ1OT1在OS细胞的顺铂耐药性中的功能和机制。我们证明在耐顺铂的OS组织和细胞系中KCNQ1OT1水平上调。此外，敲除KCNQ1OT1可抑制骨肉瘤143B细胞的细胞增殖，迁移和侵袭，并降低顺铂耐药性。此外，生物信息学分析和双荧光素酶报告基因检测结果表明，miR-335-5p直接靶向KCNQ1OT1和β-cateninmRNA的3'-UTR，提示KCNQ1OT1通过miR-335-5p的内源性海绵调节β-catenin的表达。总体而言，KCNQ1OT1通过miR-335-5p /β-catenin轴调节OS中的顺铂耐药性，表明KCNQ1OT1通过将miR-335-5p吸附在耐顺铂的OS中诱导β-catenin表达，从而加重OS进程和对顺铂的化学耐药性。细胞，为化学耐药性OS的治疗提供理论依据。