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Abstract
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.
Highlights
Supplementary information The online version of this article contains supplementary material, which is available to authorized users.Hepatocellular carcinoma (HCC) is a common malignancy that is one of the most frequent causes of cancer-related deaths around the world
The expression levels of Sphingosine-1-phosphate receptor 1 (S1PR1), p-PI3K, PI3K, Fig. 5 KCNQ1OT1 regulates HCC tumorigenesis by regulating the PI3K/AKT signalling pathway. a The protein expression of S1PR1, p-PI3K, PI3K, p-AKT and AKT in SMMC-7721 and Huh7 cells transfected with sh-KCNQ1OT1 was measured by western blot assay. b Quantification of the results presented in a. c The protein expression of S1PR1, p-PI3K, PI3K, p-AKT and AKT in SMMC
We showed that KCNQ1OT1 and S1PR1 expression was higher in the human HCC cell lines Bel7402, HepG2, SMMC-7721 and Huh7 than in the normal human hepatic cell line WRL68 (Fig. 1a, c)
Summary
The treatments and prognosis of patients with HCC present challenges because they vary by the stage of disease, the specifics of tumour histology, the likelihood to tolerate surgery and the availability of liver transplants. Curative therapies such as liver transplantation or surgical resection are feasible in 20–40% of patients [1]. Long noncoding RNAs (lncRNAs) are involved in various aspects of gene regulation, such as mRNA splicing and translation, chromosome dosage compensation and nuclear and cytoplasmic trafficking [2,3,4,5]. Zhu and colleagues found that KCNQ1OT1 was increased in the plasma of patients with diabetic nephropathy and high-glucose (HG)-induced HK-2 cells and that
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