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Hsa_Circ_0098181 Suppresses Hepatocellular Carcinoma by Sponging miR-18a-3p and Targeting PPARA

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, and its incidence is still high in China. This study aimed to investigate the circular RNAs (circRNAs) involved in the development of HCC and elucidate the mechanism. RNA sequencing found 72 downregulated circRNAs...

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Autores principales: Luo, Yuan-Yuan, Tao, Ke-Gong, Lu, Yi-Ting, Li, Bin-Bin, Wu, Kai-Ming, Ding, Chen-Hong, Yan, Fang-Zhi, Liu, Yue, Lin, Yong, Zhang, Xin, Zeng, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899401/
https://www.ncbi.nlm.nih.gov/pubmed/35264957
http://dx.doi.org/10.3389/fphar.2022.819735
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author Luo, Yuan-Yuan
Tao, Ke-Gong
Lu, Yi-Ting
Li, Bin-Bin
Wu, Kai-Ming
Ding, Chen-Hong
Yan, Fang-Zhi
Liu, Yue
Lin, Yong
Zhang, Xin
Zeng, Xin
author_facet Luo, Yuan-Yuan
Tao, Ke-Gong
Lu, Yi-Ting
Li, Bin-Bin
Wu, Kai-Ming
Ding, Chen-Hong
Yan, Fang-Zhi
Liu, Yue
Lin, Yong
Zhang, Xin
Zeng, Xin
author_sort Luo, Yuan-Yuan
collection PubMed
description Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, and its incidence is still high in China. This study aimed to investigate the circular RNAs (circRNAs) involved in the development of HCC and elucidate the mechanism. RNA sequencing found 72 downregulated circRNAs and 88 upregulated circRNAs in human HCC tissues, including hsa_circ_0098181, hsa_circ_0072309, hsa_circ_0000831, and hsa_circ_0000231. The reduction of hsa_circ_0098181 was confirmed in eight paired human HCC tissues, hepatoma cell lines, and CCL4/DEN-induced mouse HCC models by RT-qPCR. The FISH assay revealed that hsa_circ_0098181 is mainly located in the cytoplasm of hepatocytes in the paratumor tissues. Further log-rank analysis performed in 91 HCC patients demonstrated that low expression of hsa_circ_0098181 was related to poor prognosis. The plasmid and lentivirus overexpressing hsa_circ_0098181 were delivered into HCC cell lines. After hsa_circ_0098181 was upregulated, the proliferation, invasion, migration, and colony formation of HCC cell lines were inhibited, and the apoptosis was promoted. Moreover, exogenous hsa_circ_0098181 delivery mitigated the tumor formation ability of Huh7 in Balb/C nude mice. The dual-luciferase reporter assay and the RIP assay verified that hsa_circ_0098181 sponged miR-18a-3p to regulate PPARA. In addition, a rescue experiment found miR-18a-3p mimic partly reversed the suppression of hsa_circ_0098181 on proliferation, invasion, and migration of HCC cell lines. In conclusion, hsa_circ_0098181 can repress the development of HCC through sponging miR-18a-3p and promoting the expression of PPARA in vitro and in vivo, and hsa_circ_0098181 might be a therapeutic target for HCC.
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spelling pubmed-88994012022-03-08 Hsa_Circ_0098181 Suppresses Hepatocellular Carcinoma by Sponging miR-18a-3p and Targeting PPARA Luo, Yuan-Yuan Tao, Ke-Gong Lu, Yi-Ting Li, Bin-Bin Wu, Kai-Ming Ding, Chen-Hong Yan, Fang-Zhi Liu, Yue Lin, Yong Zhang, Xin Zeng, Xin Front Pharmacol Pharmacology Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, and its incidence is still high in China. This study aimed to investigate the circular RNAs (circRNAs) involved in the development of HCC and elucidate the mechanism. RNA sequencing found 72 downregulated circRNAs and 88 upregulated circRNAs in human HCC tissues, including hsa_circ_0098181, hsa_circ_0072309, hsa_circ_0000831, and hsa_circ_0000231. The reduction of hsa_circ_0098181 was confirmed in eight paired human HCC tissues, hepatoma cell lines, and CCL4/DEN-induced mouse HCC models by RT-qPCR. The FISH assay revealed that hsa_circ_0098181 is mainly located in the cytoplasm of hepatocytes in the paratumor tissues. Further log-rank analysis performed in 91 HCC patients demonstrated that low expression of hsa_circ_0098181 was related to poor prognosis. The plasmid and lentivirus overexpressing hsa_circ_0098181 were delivered into HCC cell lines. After hsa_circ_0098181 was upregulated, the proliferation, invasion, migration, and colony formation of HCC cell lines were inhibited, and the apoptosis was promoted. Moreover, exogenous hsa_circ_0098181 delivery mitigated the tumor formation ability of Huh7 in Balb/C nude mice. The dual-luciferase reporter assay and the RIP assay verified that hsa_circ_0098181 sponged miR-18a-3p to regulate PPARA. In addition, a rescue experiment found miR-18a-3p mimic partly reversed the suppression of hsa_circ_0098181 on proliferation, invasion, and migration of HCC cell lines. In conclusion, hsa_circ_0098181 can repress the development of HCC through sponging miR-18a-3p and promoting the expression of PPARA in vitro and in vivo, and hsa_circ_0098181 might be a therapeutic target for HCC. Frontiers Media S.A. 2022-02-21 /pmc/articles/PMC8899401/ /pubmed/35264957 http://dx.doi.org/10.3389/fphar.2022.819735 Text en Copyright © 2022 Luo, Tao, Lu, Li, Wu, Ding, Yan, Liu, Lin, Zhang and Zeng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Luo, Yuan-Yuan
Tao, Ke-Gong
Lu, Yi-Ting
Li, Bin-Bin
Wu, Kai-Ming
Ding, Chen-Hong
Yan, Fang-Zhi
Liu, Yue
Lin, Yong
Zhang, Xin
Zeng, Xin
Hsa_Circ_0098181 Suppresses Hepatocellular Carcinoma by Sponging miR-18a-3p and Targeting PPARA
title Hsa_Circ_0098181 Suppresses Hepatocellular Carcinoma by Sponging miR-18a-3p and Targeting PPARA
title_full Hsa_Circ_0098181 Suppresses Hepatocellular Carcinoma by Sponging miR-18a-3p and Targeting PPARA
title_fullStr Hsa_Circ_0098181 Suppresses Hepatocellular Carcinoma by Sponging miR-18a-3p and Targeting PPARA
title_full_unstemmed Hsa_Circ_0098181 Suppresses Hepatocellular Carcinoma by Sponging miR-18a-3p and Targeting PPARA
title_short Hsa_Circ_0098181 Suppresses Hepatocellular Carcinoma by Sponging miR-18a-3p and Targeting PPARA
title_sort hsa_circ_0098181 suppresses hepatocellular carcinoma by sponging mir-18a-3p and targeting ppara
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899401/
https://www.ncbi.nlm.nih.gov/pubmed/35264957
http://dx.doi.org/10.3389/fphar.2022.819735
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