The aim of this study was to investigate the effect of lncRNA KCNQ1OT1 on HCC and to explore the possible underlying mechanisms. The expression levels of KCNQ1OT1, miR-149 and S1PR1 were detected by qRT-PCR assay. A dual luciferase reporter assay was used to detect the interaction between KCNQ1OT1 and miR-149, as well as miR-149 and S1PR1. The interaction between KCNQ1OT1 and miR-149 was further investigated by RNA pull-down assay. Wound healing assays and Transwell assays were carried out to determine cell migration and invasion. A xenograft tumour assay was used to validate the role of KCNQ1OT1 in vivo. KCNQ1OT1 and S1PR1 were significantly increased, but miR-149 was decreased in HCC cells. Luciferase reporter assays and RNA pull-down assays revealed that KCNQ1OT1 directly targeted miR-149. In addition, miR-149 bound to the 3’-UTR of S1PR1. Knockdown of KCNQ1OT1 or overexpression of miR-149 inhibited the invasion and migration of HCC cells. However, suppression of miR-149 could abrogate the effect of KCNQ1OT1 knockdown on the invasion and migration abilities of HCC cells. In vivo assays showed that KCNQ1OT1 knockdown suppressed tumour growth. This work suggests that lncRNA KCNQ1OT1 might act as a potential therapeutic target in HCC.

本研究的目的是研究 lncRNA KCNQ1OT1 对 HCC 的影响，并探索可能的潜在机制。qRT-PCR法检测KCNQ1OT1、miR-149和S1PR1的表达水平。双荧光素酶报告基因检测用于检测 KCNQ1OT1 和 miR-149 以及 miR-149 和 S1PR1 之间的相互作用。通过RNA pull-down测定进一步研究了KCNQ1OT1和miR-149之间的相互作用。进行伤口愈合测定和 Transwell 测定以确定细胞迁移和侵袭。异种移植肿瘤试验用于验证 KCNQ1OT1 在体内的作用。HCC细胞中KCNQ1OT1和S1PR1显着增加，但miR-149减少。荧光素酶报告基因分析和 RNA 下拉分析显示 KCNQ1OT1 直接靶向 miR-149。此外，miR-149 与 S1PR1 的 3'-UTR 结合。敲低 KCNQ1OT1 或过表达 miR-149 可抑制 HCC 细胞的侵袭和迁移。然而，抑制 miR-149 可以消除 KCNQ1OT1 敲低对 HCC 细胞侵袭和迁移能力的影响。体内试验表明，KCNQ1OT1 敲低抑制了肿瘤生长。这项工作表明 lncRNA KCNQ1OT1 可能作为 HCC 的潜在治疗靶点。