Department of Chinese Medicine, Affiliated Longhua Central Hospital, Guangdong Medical University, Shenzhen, 518110, Guangdong, China.
Department of Quality Control, Affiliated Longhua Central Hospital, Guangdong Medical University, Shenzhen, 518110, Guangdong, China.
Biochem Biophys Res Commun. 2018 Sep 18;503(4):2400-2406. doi: 10.1016/j.bbrc.2018.06.168. Epub 2018 Jul 4.
The underlying functions of long non-coding RNAs (lncRNAs) on chemoresistance in multiple cancers have been testified. However, the function and mechanism of lncRNAs on chemoresistance in hepatocellular carcinoma are still confused. In this study, we concentrated on the function and mechanism of KCNQ1OT1 on oxaliplatin resistance in hepatocellular carcinoma. Results showed that KCNQ1OT1 was significantly up-regulated in oxaliplatin-resistant HepG2 and Huh7 cells. Moreover, knockdown of KCNQ1OT1 inhibited the cell proliferation, migration, invasion and reduced the expression of drug-resistant gene (MRP5, MDR1, LRP1). Additionally, bioinformatics analysis and dual-luciferase reporter assay showed that miR-7-5p directly targeted the 3'-UTR of miR-7-5p and ABCC1 mRNA, indicating that KCNQ1OT1 regulated the expression of ABCC1 via endogenous sponging miR-7-5p. Conclusively, KCNQ1OT1 modulated oxaliplatin resistance in hepatocellular carcinoma through miR-7-5p/ABCC1 axis, indicating a novel approach for the treatment of hepatocellular carcinoma.
长链非编码 RNA（lncRNA）在多种癌症的化疗耐药中的潜在功能已得到证实。然而，lncRNA 在肝癌化疗耐药中的功能和机制仍存在混淆。在本研究中，我们集中研究了 KCNQ1OT1 在肝癌细胞对奥沙利铂耐药中的功能和机制。结果表明，KCNQ1OT1 在奥沙利铂耐药的 HepG2 和 Huh7 细胞中显著上调。此外，敲低 KCNQ1OT1 抑制了细胞增殖、迁移和侵袭，并降低了耐药基因（MRP5、MDR1、LRP1）的表达。此外，生物信息学分析和双荧光素酶报告基因实验表明，miR-7-5p 可以直接靶向 miR-7-5p 和 ABCC1 mRNA 的 3'-UTR，表明 KCNQ1OT1 通过内源性海绵 miR-7-5p 调节 ABCC1 的表达。综上所述，KCNQ1OT1 通过 miR-7-5p/ABCC1 轴调节肝癌细胞对奥沙利铂的耐药性，为肝癌的治疗提供了一种新方法。
