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LncRNA KCNQ1OT1 regulates the invasion and migration of hepatocellular carcinoma by acting on S1PR1 through miR-149

Cancer Gene Therapy volume 28, pages 850–863 (2021)Cite this article

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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.

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Fig. 1: The expression levels of KCNQ1OT1, miR-149 and S1PR1 in normal human hepatocytes and hepatocellular carcinoma (HCC) cells.
Fig. 2: The interactions between lncRNA KCNQ1OT1 and miR-149, miR-149 and S1PR1.
Fig. 3: LncRNA KCNQ1OT1 knockdown inhibits the migration and invasion ability of HCC cells.
Fig. 4: The overexpression of miR-149 inhibits the migration and invasion ability of HCC cells.
Fig. 5: KCNQ1OT1 regulates HCC tumorigenesis by regulating the PI3K/AKT signalling pathway.
Fig. 6: sh-KCNQ1OT1 was co-transfected with miR-149 inhibitor to reverse the effect of sh-KCNQ1OT1 on the migration and invasion of HCC cells.
Fig. 7: The effect of KCNQ1OT1 knockdown on tumour growth in vivo.

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All data generated or analysed during this study are included in this published article.

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Acknowledgements

This work was supported by the PhD Start-up Fund of Guangdong Medical University (No.: 2XB17025), Medical Scientific Research Foundation of Guangdong Province of China (No.: B2019024), Project of Traditional Chinese Medicine Bureau of Guangdong Province of China (No.: 20202095) and “Group-type” Special Support Project for Education Talents in Universities (No.: 4SG19045G).

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Authors and Affiliations

  1. School of Pharmacy, Guangdong Medical University, 523808, Dongguan, P.R. China

    Ji-Lun Cheng

  2. Department of Pathology, Henan Provincial People’s Hospital, 453000, Zhengzhou, P.R. China

    Du-Juan Li

  3. Department of Emergency Intensive Care Unit, General Hospital of Pingmei Shenma Medical Group, 467200, Pingdingshan, P.R. China

    Ming-Yang Lv

  4. Department of Physiology, Guangdong Medical University, 523808, Dongguan, P.R. China

    Yi-Jin Pei, Xiu-Juan Zhang & Ai-Hui Fan

  5. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, 510515, Guangzhou, P.R. China

    Lin Li

  6. Guangdong Medical University, 523808, Dongguan, P.R. China

    Xiang-Yu Liu

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Contributions

Guarantor of integrity of the entire study and study concepts: A-HF. Study design: J-LC, D-JL, M-YL, LL. Definition of intellectual content: A-HF, D-JL. Literature research: D-JL, X-YL. Clinical studies: D-JL, M-YL. Experimental studies and data acquisition: J-LC, M-YL. Data analysis and statistical analysis: Y-JP. Manuscript preparation: J-LC, D-JL. Manuscript editing and manuscript review: X-JZ, A-HF.

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Correspondence to Ai-Hui Fan.

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The informed consent was obtained from the study participants.

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The protocol has been approved by the Ethics Committee of Guangdong Medical University. All patients were informed of the study and signed the written consent.

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Cheng, JL., Li, DJ., Lv, MY. et al. LncRNA KCNQ1OT1 regulates the invasion and migration of hepatocellular carcinoma by acting on S1PR1 through miR-149. Cancer Gene Ther 28, 850–863 (2021). https://doi.org/10.1038/s41417-020-0203-x

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