Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1784663906675851264 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8899401 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT luoyuanyuan hsacirc0098181suppresseshepatocellularcarcinomabyspongingmir18a3pandtargetingppara AT taokegong hsacirc0098181suppresseshepatocellularcarcinomabyspongingmir18a3pandtargetingppara AT luyiting hsacirc0098181suppresseshepatocellularcarcinomabyspongingmir18a3pandtargetingppara AT libinbin hsacirc0098181suppresseshepatocellularcarcinomabyspongingmir18a3pandtargetingppara AT wukaiming hsacirc0098181suppresseshepatocellularcarcinomabyspongingmir18a3pandtargetingppara AT dingchenhong hsacirc0098181suppresseshepatocellularcarcinomabyspongingmir18a3pandtargetingppara AT yanfangzhi hsacirc0098181suppresseshepatocellularcarcinomabyspongingmir18a3pandtargetingppara AT liuyue hsacirc0098181suppresseshepatocellularcarcinomabyspongingmir18a3pandtargetingppara AT linyong hsacirc0098181suppresseshepatocellularcarcinomabyspongingmir18a3pandtargetingppara AT zhangxin hsacirc0098181suppresseshepatocellularcarcinomabyspongingmir18a3pandtargetingppara AT zengxin hsacirc0098181suppresseshepatocellularcarcinomabyspongingmir18a3pandtargetingppara |