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J Cancer 2023; 14(12):2329-2343. doi:10.7150/jca.85335 This issue Cite

Research Paper

LncRNA HOTAIR Enhances Epithelial-to-mesenchymal Transition to Promote the Migration and Invasion of Liver Cancer by Regulating NUAK1 via Epigenetic Inhibition miR-145-5p Expression

Dong-xia Chu1#, Yu Jin1#, Bing-rong Wang1, Yan Jiao2, Chao-ke Zhang1, Zi-han Guo1, Shao-zhuo Hu1, Na Li1✉

1. Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, 130021, P.R. China.
2. Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, P.R. China.
# Contributed equally to this work.

✉ Corresponding author: Na Li, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, Jilin 130012, P.R. China. Email: lina721030edu.cn.

Citation:
Chu Dx, Jin Y, Wang Br, Jiao Y, Zhang Ck, Guo Zh, Hu Sz, Li N. LncRNA HOTAIR Enhances Epithelial-to-mesenchymal Transition to Promote the Migration and Invasion of Liver Cancer by Regulating NUAK1 via Epigenetic Inhibition miR-145-5p Expression. J Cancer 2023; 14(12):2329-2343. doi:10.7150/jca.85335. https://www.jcancer.org/v14p2329.htm
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Abstract

Graphic abstract

LncRNA HOTAIR play important roles in the epigenetic regulation of carcinogenesis and progression in liver cancer. Previous studies suggest that the overexpression of HOTAIR predicts poor prognosis. In this study, through transcriptome sequencing data and in vitro experiments, we found that HOTAIR were more highly expressed and there is significantly positive relationship between HOTAIR and NUAK1 in liver cancer tissues and cell lines. miR-145-5p was downregulated and showed negative correlation with HOTAIR and NUAK1. Transfect Sh-HOTAIR, LZRS-HOTAIR, miR-145 mimic, miR-145 inhibitor to change the expression of HOTAIR and miR-145-5p. The addition of HTH-01-015 inhibits the expression of NUAK1. HOTAIR knockdown, miR-145-5p upregulation and NUAK1 inhibition all repressed migration, invasion and metastasis and reversed the epithelial-to-mesenchymal transition in SNU-387 and HepG2 cells. We also showed that HOTAIR recruiting and binding PRC2 (EZH2) epigenetically represses miR-145-5p, which controls the target NUAK1, thus contributing to liver cancer cell-EMT process and accelerating tumor metastasis. Moreover, it is demonstrated that HOTAIR crosstalk with miR-145-5p/NUAK1 during epigenetic regulation. Our findings indicate that HOTAIR/miR-145-5p/NUAK1 axis acts as an EMT regulator and may be candidate prognostic biomarker and targets for new therapies in liver cancer.

Keywords: liver cancer, HOTAIR, miR-145-5p, NUAK1, EMT

Citation styles

APA
Chu, D.x., Jin, Y., Wang, B.r., Jiao, Y., Zhang, C.k., Guo, Z.h., Hu, S.z., Li, N. (2023). LncRNA HOTAIR Enhances Epithelial-to-mesenchymal Transition to Promote the Migration and Invasion of Liver Cancer by Regulating NUAK1 via Epigenetic Inhibition miR-145-5p Expression. Journal of Cancer, 14(12), 2329-2343. https://doi.org/10.7150/jca.85335.

ACS
Chu, D.x.; Jin, Y.; Wang, B.r.; Jiao, Y.; Zhang, C.k.; Guo, Z.h.; Hu, S.z.; Li, N. LncRNA HOTAIR Enhances Epithelial-to-mesenchymal Transition to Promote the Migration and Invasion of Liver Cancer by Regulating NUAK1 via Epigenetic Inhibition miR-145-5p Expression. J. Cancer 2023, 14 (12), 2329-2343. DOI: 10.7150/jca.85335.

NLM
Chu Dx, Jin Y, Wang Br, Jiao Y, Zhang Ck, Guo Zh, Hu Sz, Li N. LncRNA HOTAIR Enhances Epithelial-to-mesenchymal Transition to Promote the Migration and Invasion of Liver Cancer by Regulating NUAK1 via Epigenetic Inhibition miR-145-5p Expression. J Cancer 2023; 14(12):2329-2343. doi:10.7150/jca.85335. https://www.jcancer.org/v14p2329.htm

CSE
Chu Dx, Jin Y, Wang Br, Jiao Y, Zhang Ck, Guo Zh, Hu Sz, Li N. 2023. LncRNA HOTAIR Enhances Epithelial-to-mesenchymal Transition to Promote the Migration and Invasion of Liver Cancer by Regulating NUAK1 via Epigenetic Inhibition miR-145-5p Expression. J Cancer. 14(12):2329-2343.

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