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CircMMP9 accelerates the progression of hepatocellular carcinoma through the miR-149/CCND2 axis

BACKGROUND: This study aimed to verify the hypothesis that circular RNA MMP9 (circMMP9) promotes hepatocellular carcinoma (HCC) progression through targeting miR-149 and regulating cyclin D2 (CCND2) expression. METHODS: Expression of circMMP9, miR-149 and CCND2 was detected by quantitative reverse t...

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Autores principales: Li, Xiaolou, Fang, Jiankai, Wei, Guangmin, Chen, Ying, Li, Dongliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9459201/
https://www.ncbi.nlm.nih.gov/pubmed/36092323
http://dx.doi.org/10.21037/jgo-22-677
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author Li, Xiaolou
Fang, Jiankai
Wei, Guangmin
Chen, Ying
Li, Dongliang
author_facet Li, Xiaolou
Fang, Jiankai
Wei, Guangmin
Chen, Ying
Li, Dongliang
author_sort Li, Xiaolou
collection PubMed
description BACKGROUND: This study aimed to verify the hypothesis that circular RNA MMP9 (circMMP9) promotes hepatocellular carcinoma (HCC) progression through targeting miR-149 and regulating cyclin D2 (CCND2) expression. METHODS: Expression of circMMP9, miR-149 and CCND2 was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or protein blotting. Cell Counting Kit-8 (CCK-8) was used to evaluate cell proliferation. The HCC cell migration and invasion were evaluated using wound healing and transwell assays. The interaction among circMMP9, miR-149, and CCND2 was evaluated using luciferase, RNA-pull down, and RNA immunoprecipitation (RIP) assays, respectively. Cell apoptosis and cycle were examined by flow cytometry. A subcutaneous HCC xenograft mouse model was established for analyzing the role of circMMP9 in regulating the progression of HCC in vivo. RESULTS: The expression of circMMP9 was elevated in HCC tissues and its high expression correlated with poor prognosis (P<0.05). Knockdown of circMMP9 restrained the proliferation, migration, and invasion of HCC cells and led to arrested cell cycle and increased apoptosis (all P<0.05). Furthermore, knockdown of circMMP9 attenuated HCC growth in vivo (P<0.05). Mechanically, circMMP9 acted as a sponge for miR-149 and enhanced CCND2 expression in HCC cells (P<0.05). Inhibition of miR-149 or overexpression of CCND2 abrogated knockdown of circMMP9-mediated alleviation of the malignant phenotypes of HCC (P<0.05). CONCLUSIONS: For the first time, we demonstrated that circMMP9 exacerbated HCC progression through the miR-149/CCND2 axis, which suggested that circMMP9 could be potentially targeted for HCC treatment.
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spelling pubmed-94592012022-09-10 CircMMP9 accelerates the progression of hepatocellular carcinoma through the miR-149/CCND2 axis Li, Xiaolou Fang, Jiankai Wei, Guangmin Chen, Ying Li, Dongliang J Gastrointest Oncol Original Article BACKGROUND: This study aimed to verify the hypothesis that circular RNA MMP9 (circMMP9) promotes hepatocellular carcinoma (HCC) progression through targeting miR-149 and regulating cyclin D2 (CCND2) expression. METHODS: Expression of circMMP9, miR-149 and CCND2 was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or protein blotting. Cell Counting Kit-8 (CCK-8) was used to evaluate cell proliferation. The HCC cell migration and invasion were evaluated using wound healing and transwell assays. The interaction among circMMP9, miR-149, and CCND2 was evaluated using luciferase, RNA-pull down, and RNA immunoprecipitation (RIP) assays, respectively. Cell apoptosis and cycle were examined by flow cytometry. A subcutaneous HCC xenograft mouse model was established for analyzing the role of circMMP9 in regulating the progression of HCC in vivo. RESULTS: The expression of circMMP9 was elevated in HCC tissues and its high expression correlated with poor prognosis (P<0.05). Knockdown of circMMP9 restrained the proliferation, migration, and invasion of HCC cells and led to arrested cell cycle and increased apoptosis (all P<0.05). Furthermore, knockdown of circMMP9 attenuated HCC growth in vivo (P<0.05). Mechanically, circMMP9 acted as a sponge for miR-149 and enhanced CCND2 expression in HCC cells (P<0.05). Inhibition of miR-149 or overexpression of CCND2 abrogated knockdown of circMMP9-mediated alleviation of the malignant phenotypes of HCC (P<0.05). CONCLUSIONS: For the first time, we demonstrated that circMMP9 exacerbated HCC progression through the miR-149/CCND2 axis, which suggested that circMMP9 could be potentially targeted for HCC treatment. AME Publishing Company 2022-08 /pmc/articles/PMC9459201/ /pubmed/36092323 http://dx.doi.org/10.21037/jgo-22-677 Text en 2022 Journal of Gastrointestinal Oncology. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Li, Xiaolou
Fang, Jiankai
Wei, Guangmin
Chen, Ying
Li, Dongliang
CircMMP9 accelerates the progression of hepatocellular carcinoma through the miR-149/CCND2 axis
title CircMMP9 accelerates the progression of hepatocellular carcinoma through the miR-149/CCND2 axis
title_full CircMMP9 accelerates the progression of hepatocellular carcinoma through the miR-149/CCND2 axis
title_fullStr CircMMP9 accelerates the progression of hepatocellular carcinoma through the miR-149/CCND2 axis
title_full_unstemmed CircMMP9 accelerates the progression of hepatocellular carcinoma through the miR-149/CCND2 axis
title_short CircMMP9 accelerates the progression of hepatocellular carcinoma through the miR-149/CCND2 axis
title_sort circmmp9 accelerates the progression of hepatocellular carcinoma through the mir-149/ccnd2 axis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9459201/
https://www.ncbi.nlm.nih.gov/pubmed/36092323
http://dx.doi.org/10.21037/jgo-22-677
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