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CircRNA hsa_circ_0110102 inhibited macrophage activation and hepatocellular carcinoma progression via miR-580-5p/PPARα/CCL2 pathway

Circular RNAs (circRNAs) have critical regulatory roles in tumor biology. However, their contributions in hepatocellular carcinoma (HCC) still remain enigmatic. The present study aimed to investigate the molecular mechanisms underlying the involvement of hsa_circ_0110102 in the occurrence and develo...

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Autores principales: Wang, Xinxing, Sheng, Wei, Xu, Tao, Xu, Jiawen, Gao, Ruyi, Zhang, Zhenhai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109088/
https://www.ncbi.nlm.nih.gov/pubmed/33891564
http://dx.doi.org/10.18632/aging.202900
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author Wang, Xinxing
Sheng, Wei
Xu, Tao
Xu, Jiawen
Gao, Ruyi
Zhang, Zhenhai
author_facet Wang, Xinxing
Sheng, Wei
Xu, Tao
Xu, Jiawen
Gao, Ruyi
Zhang, Zhenhai
author_sort Wang, Xinxing
collection PubMed
description Circular RNAs (circRNAs) have critical regulatory roles in tumor biology. However, their contributions in hepatocellular carcinoma (HCC) still remain enigmatic. The present study aimed to investigate the molecular mechanisms underlying the involvement of hsa_circ_0110102 in the occurrence and development of HCC. The expression level of hsa_circ_0110102 was significantly downregulated in HCC cell lines and tissues, which was associated with poor prognosis. Knockdown hsa_circ_0110102 significantly promoted cell proliferation, migration, and invasion. Moreover, the interaction between hsa_circ_0110102 and miR-580-5p was predicted and verified by luciferase assay and RNA pull-down. The findings indicated that hsa_circ_0110102 functioned as a sponge for miR-580-5p. Moreover, miR-580-5p directly bound to the 3′ UTR of PPARα, which decreased the production and release of C-C chemokine ligand 2 (CCL2) in HCC cells. CCL2 could activate the cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) pathway in macrophage via FoxO1 in a p38 MAPK–dependent manner. Furthermore, the Δ256 mutant of FoxO1 showed no activation effect. These results concluded that hsa_circ_0110102 acted as a sponge for miR-580-5p and inhibited CCL2 secretion into tumor microenvironment by decrease the expression of PPARα in HCC cells, then inhibited the pro-inflammatory cytokine release from macrophages by regulating the COX-2/PGE2 pathway. In conclusion, hsa_circ_0110102 served as a potential prognostic predictor or therapeutic target for HCC.
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spelling pubmed-81090882021-05-12 CircRNA hsa_circ_0110102 inhibited macrophage activation and hepatocellular carcinoma progression via miR-580-5p/PPARα/CCL2 pathway Wang, Xinxing Sheng, Wei Xu, Tao Xu, Jiawen Gao, Ruyi Zhang, Zhenhai Aging (Albany NY) Research Paper Circular RNAs (circRNAs) have critical regulatory roles in tumor biology. However, their contributions in hepatocellular carcinoma (HCC) still remain enigmatic. The present study aimed to investigate the molecular mechanisms underlying the involvement of hsa_circ_0110102 in the occurrence and development of HCC. The expression level of hsa_circ_0110102 was significantly downregulated in HCC cell lines and tissues, which was associated with poor prognosis. Knockdown hsa_circ_0110102 significantly promoted cell proliferation, migration, and invasion. Moreover, the interaction between hsa_circ_0110102 and miR-580-5p was predicted and verified by luciferase assay and RNA pull-down. The findings indicated that hsa_circ_0110102 functioned as a sponge for miR-580-5p. Moreover, miR-580-5p directly bound to the 3′ UTR of PPARα, which decreased the production and release of C-C chemokine ligand 2 (CCL2) in HCC cells. CCL2 could activate the cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) pathway in macrophage via FoxO1 in a p38 MAPK–dependent manner. Furthermore, the Δ256 mutant of FoxO1 showed no activation effect. These results concluded that hsa_circ_0110102 acted as a sponge for miR-580-5p and inhibited CCL2 secretion into tumor microenvironment by decrease the expression of PPARα in HCC cells, then inhibited the pro-inflammatory cytokine release from macrophages by regulating the COX-2/PGE2 pathway. In conclusion, hsa_circ_0110102 served as a potential prognostic predictor or therapeutic target for HCC. Impact Journals 2021-04-23 /pmc/articles/PMC8109088/ /pubmed/33891564 http://dx.doi.org/10.18632/aging.202900 Text en Copyright: © 2021 Wang et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Wang, Xinxing
Sheng, Wei
Xu, Tao
Xu, Jiawen
Gao, Ruyi
Zhang, Zhenhai
CircRNA hsa_circ_0110102 inhibited macrophage activation and hepatocellular carcinoma progression via miR-580-5p/PPARα/CCL2 pathway
title CircRNA hsa_circ_0110102 inhibited macrophage activation and hepatocellular carcinoma progression via miR-580-5p/PPARα/CCL2 pathway
title_full CircRNA hsa_circ_0110102 inhibited macrophage activation and hepatocellular carcinoma progression via miR-580-5p/PPARα/CCL2 pathway
title_fullStr CircRNA hsa_circ_0110102 inhibited macrophage activation and hepatocellular carcinoma progression via miR-580-5p/PPARα/CCL2 pathway
title_full_unstemmed CircRNA hsa_circ_0110102 inhibited macrophage activation and hepatocellular carcinoma progression via miR-580-5p/PPARα/CCL2 pathway
title_short CircRNA hsa_circ_0110102 inhibited macrophage activation and hepatocellular carcinoma progression via miR-580-5p/PPARα/CCL2 pathway
title_sort circrna hsa_circ_0110102 inhibited macrophage activation and hepatocellular carcinoma progression via mir-580-5p/pparα/ccl2 pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109088/
https://www.ncbi.nlm.nih.gov/pubmed/33891564
http://dx.doi.org/10.18632/aging.202900
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