Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis

Lidocaine can inhibit the malignant development of various human cancers. Circular RNA (circRNA) dynein 1 heavy chain gene (circ_DYNC1H1) acted as a pro-cancer molecule in hepatocellular carcinoma (HCC). This study aimed to explore whether the function of lidocaine was related to the oncogenic circ_...

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Autores principales: Liu Hua, Cheng Jing, Xu Heng, Wan Zhenzhen
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Publicado: De Gruyter 2021
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spelling oai:doaj.org-article:1524ad15118643d8a3686863d1a8750b2021-12-05T14:10:41ZLidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis2391-541210.1515/biol-2021-0072https://doaj.org/article/1524ad15118643d8a3686863d1a8750b2021-08-01T00:00:00Zhttps://doi.org/10.1515/biol-2021-0072https://doaj.org/toc/2391-5412Lidocaine can inhibit the malignant development of various human cancers. Circular RNA (circRNA) dynein 1 heavy chain gene (circ_DYNC1H1) acted as a pro-cancer molecule in hepatocellular carcinoma (HCC). This study aimed to explore whether the function of lidocaine was related to the oncogenic circ_DYNC1H1 in HCC. Colony formation assay and 3-(4,5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay were used for proliferation detection. Cell apoptosis was assessed by flow cytometry, and migration or invasion was determined by the transwell assay. The levels of circ_DYNC1H1, microRNA-520a-3p (miR-520a-3p), and ubiquitin-specific protease 14 (USP14) were examined using the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Protein levels were measured using western blot. The binding between miR-520a-3p and circ_DYNC1H1 or USP14 was confirmed by the dual-luciferase reporter assay. In vivo assay was conducted by a xenograft model in mice. Lidocaine reduced proliferation, migration, and invasion but promoted apoptosis in HCC cells. The circ_DYNC1H1 expression was downregulated in lidocaine-treated HCC cells. The inhibitory effect of lidocaine on HCC progression was weakened after circ_DYNC1H1 overexpression. miR-520a-3p was a target of circ_DYNC1H1, and the function of lidocaine was related to the regulation of circ_DYNC1H1/miR-520a-3p axis. USP14 served as a target for miR-520a-3p, and circ_DYNC1H1 could sponge miR-520a-3p to regulate the USP14 expression. The lidocaine-induced suppression of HCC development was also achieved by mediating the miR-520a-3p/USP14 axis. In vivo assay revealed that lidocaine suppressed the tumor growth of HCC by reducing the expression of circ_DYNC1H1 to affect the levels of miR-520a-3p and USP14. Our results clarified that lidocaine impeded tumor progression via targeting the circ_DYNC1H1/miR-520a-3p/USP14 axis in HCC cells.Liu HuaCheng JingXu HengWan ZhenzhenDe Gruyterarticlecirc_dync1h1lidocainehepatocellular carcinomamir-520a-3pusp14Biology (General)QH301-705.5ENOpen Life Sciences, Vol 16, Iss 1, Pp 766-780 (2021)
institution DOAJ
collection DOAJ
language EN
topic circ_dync1h1
lidocaine
hepatocellular carcinoma
mir-520a-3p
usp14
Biology (General)
QH301-705.5
spellingShingle circ_dync1h1
lidocaine
hepatocellular carcinoma
mir-520a-3p
usp14
Biology (General)
QH301-705.5
Liu Hua
Cheng Jing
Xu Heng
Wan Zhenzhen
Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis
description Lidocaine can inhibit the malignant development of various human cancers. Circular RNA (circRNA) dynein 1 heavy chain gene (circ_DYNC1H1) acted as a pro-cancer molecule in hepatocellular carcinoma (HCC). This study aimed to explore whether the function of lidocaine was related to the oncogenic circ_DYNC1H1 in HCC. Colony formation assay and 3-(4,5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay were used for proliferation detection. Cell apoptosis was assessed by flow cytometry, and migration or invasion was determined by the transwell assay. The levels of circ_DYNC1H1, microRNA-520a-3p (miR-520a-3p), and ubiquitin-specific protease 14 (USP14) were examined using the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Protein levels were measured using western blot. The binding between miR-520a-3p and circ_DYNC1H1 or USP14 was confirmed by the dual-luciferase reporter assay. In vivo assay was conducted by a xenograft model in mice. Lidocaine reduced proliferation, migration, and invasion but promoted apoptosis in HCC cells. The circ_DYNC1H1 expression was downregulated in lidocaine-treated HCC cells. The inhibitory effect of lidocaine on HCC progression was weakened after circ_DYNC1H1 overexpression. miR-520a-3p was a target of circ_DYNC1H1, and the function of lidocaine was related to the regulation of circ_DYNC1H1/miR-520a-3p axis. USP14 served as a target for miR-520a-3p, and circ_DYNC1H1 could sponge miR-520a-3p to regulate the USP14 expression. The lidocaine-induced suppression of HCC development was also achieved by mediating the miR-520a-3p/USP14 axis. In vivo assay revealed that lidocaine suppressed the tumor growth of HCC by reducing the expression of circ_DYNC1H1 to affect the levels of miR-520a-3p and USP14. Our results clarified that lidocaine impeded tumor progression via targeting the circ_DYNC1H1/miR-520a-3p/USP14 axis in HCC cells.
format article
author Liu Hua
Cheng Jing
Xu Heng
Wan Zhenzhen
author_facet Liu Hua
Cheng Jing
Xu Heng
Wan Zhenzhen
author_sort Liu Hua
title Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis
title_short Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis
title_full Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis
title_fullStr Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis
title_full_unstemmed Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis
title_sort lidocaine has antitumor effect on hepatocellular carcinoma via the circ_dync1h1/mir-520a-3p/usp14 axis
publisher De Gruyter
publishDate 2021
url https://doaj.org/article/1524ad15118643d8a3686863d1a8750b
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AT xuheng lidocainehasantitumoreffectonhepatocellularcarcinomaviathecircdync1h1mir520a3pusp14axis
AT wanzhenzhen lidocainehasantitumoreffectonhepatocellularcarcinomaviathecircdync1h1mir520a3pusp14axis
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