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CircUBAP2 Promotes MMP9-Mediated Oncogenic Effect via Sponging miR-194-3p in Hepatocellular Carcinoma

BACKGROUND: The physiological regulatory functions of circRNAs have become a topic of intensive research in recent years. Increasing evidence supports a significant role of circRNAs during cancer initiation and progression, including hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A bioinform...

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Autores principales: Liu, Boqiang, Tian, Yuanshi, Chen, Mingyu, Shen, Hao, Xia, Jiafeng, Nan, Junjie, Yan, Tingting, Wang, Yifan, Shi, Liang, Shen, Bo, Yu, Hong, Cai, Xiujun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258265/
https://www.ncbi.nlm.nih.gov/pubmed/34239873
http://dx.doi.org/10.3389/fcell.2021.675043
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author Liu, Boqiang
Tian, Yuanshi
Chen, Mingyu
Shen, Hao
Xia, Jiafeng
Nan, Junjie
Yan, Tingting
Wang, Yifan
Shi, Liang
Shen, Bo
Yu, Hong
Cai, Xiujun
author_facet Liu, Boqiang
Tian, Yuanshi
Chen, Mingyu
Shen, Hao
Xia, Jiafeng
Nan, Junjie
Yan, Tingting
Wang, Yifan
Shi, Liang
Shen, Bo
Yu, Hong
Cai, Xiujun
author_sort Liu, Boqiang
collection PubMed
description BACKGROUND: The physiological regulatory functions of circRNAs have become a topic of intensive research in recent years. Increasing evidence supports a significant role of circRNAs during cancer initiation and progression, including hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A bioinformatics analysis from three independent Gene Expression Omnibus (GEO) databases was performed to profile and screen the dysregulated circRNAs in HCC. RT-qPCR was used to examine the expression level of circUBAP2 in HCC and adjacent non-tumor tissues. Then, proliferation assays (CCK8 and colony formation) and migration assays (transwell and wound healing) were performed to examine effect of circUBAP2 in vitro. Immunoprecipitation, RNA pulldown, FISH, and dual-luciferase reporter assay was conducted to explore the circUBAP2-related mechanism for regulating HCC progression. Moreover, a mouse xenograft model and a mouse lung metastasis model confirmed the effect of circUBAP2 in vivo. RESULTS: In this study, we found a novel circRNA: circUBAP2, which was identified by bioinformatics analysis. Among 91 HCC patients, circUBAP2 was significantly upregulated in HCC tissues, and negatively correlated with aggressive clinical characteristics and prognosis. Functional assays demonstrated that circUBAP2 promoted cell proliferation, colony formation, migration, and invasion in vitro. Moreover, circUBAP2 enhanced tumor growth and pulmonary metastasis in vivo. Mechanistically, circUBAP2 acts as a competing endogenous RNA (ceRNA) for miR-194-3p, a tumor suppressor in HCC. We confirmed that MMP9 was direct target for miR-194-3p, which was regulated by circUBAP2. CONCLUSION: CircUBAP2 plays a significant role in promoting HCC via the miR-194-3p/MMP9 pathway and could serve as a promising prognostic biomarker and novel therapeutic target for HCC patients.
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spelling pubmed-82582652021-07-07 CircUBAP2 Promotes MMP9-Mediated Oncogenic Effect via Sponging miR-194-3p in Hepatocellular Carcinoma Liu, Boqiang Tian, Yuanshi Chen, Mingyu Shen, Hao Xia, Jiafeng Nan, Junjie Yan, Tingting Wang, Yifan Shi, Liang Shen, Bo Yu, Hong Cai, Xiujun Front Cell Dev Biol Cell and Developmental Biology BACKGROUND: The physiological regulatory functions of circRNAs have become a topic of intensive research in recent years. Increasing evidence supports a significant role of circRNAs during cancer initiation and progression, including hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A bioinformatics analysis from three independent Gene Expression Omnibus (GEO) databases was performed to profile and screen the dysregulated circRNAs in HCC. RT-qPCR was used to examine the expression level of circUBAP2 in HCC and adjacent non-tumor tissues. Then, proliferation assays (CCK8 and colony formation) and migration assays (transwell and wound healing) were performed to examine effect of circUBAP2 in vitro. Immunoprecipitation, RNA pulldown, FISH, and dual-luciferase reporter assay was conducted to explore the circUBAP2-related mechanism for regulating HCC progression. Moreover, a mouse xenograft model and a mouse lung metastasis model confirmed the effect of circUBAP2 in vivo. RESULTS: In this study, we found a novel circRNA: circUBAP2, which was identified by bioinformatics analysis. Among 91 HCC patients, circUBAP2 was significantly upregulated in HCC tissues, and negatively correlated with aggressive clinical characteristics and prognosis. Functional assays demonstrated that circUBAP2 promoted cell proliferation, colony formation, migration, and invasion in vitro. Moreover, circUBAP2 enhanced tumor growth and pulmonary metastasis in vivo. Mechanistically, circUBAP2 acts as a competing endogenous RNA (ceRNA) for miR-194-3p, a tumor suppressor in HCC. We confirmed that MMP9 was direct target for miR-194-3p, which was regulated by circUBAP2. CONCLUSION: CircUBAP2 plays a significant role in promoting HCC via the miR-194-3p/MMP9 pathway and could serve as a promising prognostic biomarker and novel therapeutic target for HCC patients. Frontiers Media S.A. 2021-06-22 /pmc/articles/PMC8258265/ /pubmed/34239873 http://dx.doi.org/10.3389/fcell.2021.675043 Text en Copyright © 2021 Liu, Tian, Chen, Shen, Xia, Nan, Yan, Wang, Shi, Shen, Yu and Cai. 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 Cell and Developmental Biology
Liu, Boqiang
Tian, Yuanshi
Chen, Mingyu
Shen, Hao
Xia, Jiafeng
Nan, Junjie
Yan, Tingting
Wang, Yifan
Shi, Liang
Shen, Bo
Yu, Hong
Cai, Xiujun
CircUBAP2 Promotes MMP9-Mediated Oncogenic Effect via Sponging miR-194-3p in Hepatocellular Carcinoma
title CircUBAP2 Promotes MMP9-Mediated Oncogenic Effect via Sponging miR-194-3p in Hepatocellular Carcinoma
title_full CircUBAP2 Promotes MMP9-Mediated Oncogenic Effect via Sponging miR-194-3p in Hepatocellular Carcinoma
title_fullStr CircUBAP2 Promotes MMP9-Mediated Oncogenic Effect via Sponging miR-194-3p in Hepatocellular Carcinoma
title_full_unstemmed CircUBAP2 Promotes MMP9-Mediated Oncogenic Effect via Sponging miR-194-3p in Hepatocellular Carcinoma
title_short CircUBAP2 Promotes MMP9-Mediated Oncogenic Effect via Sponging miR-194-3p in Hepatocellular Carcinoma
title_sort circubap2 promotes mmp9-mediated oncogenic effect via sponging mir-194-3p in hepatocellular carcinoma
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258265/
https://www.ncbi.nlm.nih.gov/pubmed/34239873
http://dx.doi.org/10.3389/fcell.2021.675043
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