Cargando…

MiR-29c-3p Suppresses the Migration, Invasion and Cell Cycle in Esophageal Carcinoma via CCNA2/p53 Axis

OBJECTIVE: In the present study, we tried to describe the role of miR-29c-3p in esophageal carcinoma (EC) and the relationship of miR-29c-3p with CCNA2 as well as cell cycle, accordingly revealing the potential molecular mechanism across cell proliferation, migration and invasion. METHODS: Expressio...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Haiyong, Fu, Linhai, Wei, Desheng, Wang, Bin, Zhang, Chu, Zhu, Ting, Ma, Zhifeng, Li, Zhupeng, Wu, Yuanlin, Yu, Guangmao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044414/
https://www.ncbi.nlm.nih.gov/pubmed/32154226
http://dx.doi.org/10.3389/fbioe.2020.00075
_version_ 1783501565474111488
author Wang, Haiyong
Fu, Linhai
Wei, Desheng
Wang, Bin
Zhang, Chu
Zhu, Ting
Ma, Zhifeng
Li, Zhupeng
Wu, Yuanlin
Yu, Guangmao
author_facet Wang, Haiyong
Fu, Linhai
Wei, Desheng
Wang, Bin
Zhang, Chu
Zhu, Ting
Ma, Zhifeng
Li, Zhupeng
Wu, Yuanlin
Yu, Guangmao
author_sort Wang, Haiyong
collection PubMed
description OBJECTIVE: In the present study, we tried to describe the role of miR-29c-3p in esophageal carcinoma (EC) and the relationship of miR-29c-3p with CCNA2 as well as cell cycle, accordingly revealing the potential molecular mechanism across cell proliferation, migration and invasion. METHODS: Expression profiles of EC miRNAs and matched clinical data were accessed from TCGA database for differential and survival analyses. Bioinformatics databases were employed to predict the downstream targets of the potential miRNA, and enrichment analysis was performed on the miRNA and corresponding target gene using GSEA software. qRT-PCR was conducted to detect the expression levels of miR-29c-3p and CCNA2 mRNA in EC tissues and cells, and Western blot was performed for the examination of CCNA2, CDK1 and p53 protein levels. Subsequently, cells were harvested for MTT, Transwell as well as flow cytometry assays to examine cell viability, migration, invasion and cell cycle. Dual-luciferase reporter gene assay and RIP were carried out to further investigate and verify the targeted relationship between miR-29c-3p and CCNA2. RESULTS: MiR-29c-3p was shown to be significantly down-regulated in EC tissues and able to predict poor prognosis. CCNA2 was found to be a downstream target of miR-29c-3p and mainly enriched in cell cycle and p53 signaling pathway, whereas miR-29c-3p was remarkably activated in cell cycle. MiR-29c-3p overexpression inhibited cell proliferation, migration and invasion, as well as arrested cells in G0/G1 phase. As suggested by dual-luciferase reporter gene assay and RIP, CCNA2 was under the regulation of miR-29c-3p, and the negative correlation between the two genes was verified. Silencing CCNA2 could suppress cell proliferation, migration and invasion, as well as activate p53 pathway, even was seen to reverse the inhibitory effect of PFTβ on p53. Besides, in the presence of low miR-29c-3p, CCNA2 was up-regulated while p53 was simultaneously inhibited, resulting in the promotion of cell migration, invasion and cell cycle arrest. CONCLUSION: MiR-29c-3p plays a regulatory role in EC tumorigenesis and development. MiR-29c-3p can target CCNA2 to mediate p53 signaling pathway, finally attributing to the inhibition of cell proliferation, migration and invasion, and making cells arrest in G0/G1 phase.
format Online
Article
Text
id pubmed-7044414
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-70444142020-03-09 MiR-29c-3p Suppresses the Migration, Invasion and Cell Cycle in Esophageal Carcinoma via CCNA2/p53 Axis Wang, Haiyong Fu, Linhai Wei, Desheng Wang, Bin Zhang, Chu Zhu, Ting Ma, Zhifeng Li, Zhupeng Wu, Yuanlin Yu, Guangmao Front Bioeng Biotechnol Bioengineering and Biotechnology OBJECTIVE: In the present study, we tried to describe the role of miR-29c-3p in esophageal carcinoma (EC) and the relationship of miR-29c-3p with CCNA2 as well as cell cycle, accordingly revealing the potential molecular mechanism across cell proliferation, migration and invasion. METHODS: Expression profiles of EC miRNAs and matched clinical data were accessed from TCGA database for differential and survival analyses. Bioinformatics databases were employed to predict the downstream targets of the potential miRNA, and enrichment analysis was performed on the miRNA and corresponding target gene using GSEA software. qRT-PCR was conducted to detect the expression levels of miR-29c-3p and CCNA2 mRNA in EC tissues and cells, and Western blot was performed for the examination of CCNA2, CDK1 and p53 protein levels. Subsequently, cells were harvested for MTT, Transwell as well as flow cytometry assays to examine cell viability, migration, invasion and cell cycle. Dual-luciferase reporter gene assay and RIP were carried out to further investigate and verify the targeted relationship between miR-29c-3p and CCNA2. RESULTS: MiR-29c-3p was shown to be significantly down-regulated in EC tissues and able to predict poor prognosis. CCNA2 was found to be a downstream target of miR-29c-3p and mainly enriched in cell cycle and p53 signaling pathway, whereas miR-29c-3p was remarkably activated in cell cycle. MiR-29c-3p overexpression inhibited cell proliferation, migration and invasion, as well as arrested cells in G0/G1 phase. As suggested by dual-luciferase reporter gene assay and RIP, CCNA2 was under the regulation of miR-29c-3p, and the negative correlation between the two genes was verified. Silencing CCNA2 could suppress cell proliferation, migration and invasion, as well as activate p53 pathway, even was seen to reverse the inhibitory effect of PFTβ on p53. Besides, in the presence of low miR-29c-3p, CCNA2 was up-regulated while p53 was simultaneously inhibited, resulting in the promotion of cell migration, invasion and cell cycle arrest. CONCLUSION: MiR-29c-3p plays a regulatory role in EC tumorigenesis and development. MiR-29c-3p can target CCNA2 to mediate p53 signaling pathway, finally attributing to the inhibition of cell proliferation, migration and invasion, and making cells arrest in G0/G1 phase. Frontiers Media S.A. 2020-02-20 /pmc/articles/PMC7044414/ /pubmed/32154226 http://dx.doi.org/10.3389/fbioe.2020.00075 Text en Copyright © 2020 Wang, Fu, Wei, Wang, Zhang, Zhu, Ma, Li, Wu and Yu. http://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 Bioengineering and Biotechnology
Wang, Haiyong
Fu, Linhai
Wei, Desheng
Wang, Bin
Zhang, Chu
Zhu, Ting
Ma, Zhifeng
Li, Zhupeng
Wu, Yuanlin
Yu, Guangmao
MiR-29c-3p Suppresses the Migration, Invasion and Cell Cycle in Esophageal Carcinoma via CCNA2/p53 Axis
title MiR-29c-3p Suppresses the Migration, Invasion and Cell Cycle in Esophageal Carcinoma via CCNA2/p53 Axis
title_full MiR-29c-3p Suppresses the Migration, Invasion and Cell Cycle in Esophageal Carcinoma via CCNA2/p53 Axis
title_fullStr MiR-29c-3p Suppresses the Migration, Invasion and Cell Cycle in Esophageal Carcinoma via CCNA2/p53 Axis
title_full_unstemmed MiR-29c-3p Suppresses the Migration, Invasion and Cell Cycle in Esophageal Carcinoma via CCNA2/p53 Axis
title_short MiR-29c-3p Suppresses the Migration, Invasion and Cell Cycle in Esophageal Carcinoma via CCNA2/p53 Axis
title_sort mir-29c-3p suppresses the migration, invasion and cell cycle in esophageal carcinoma via ccna2/p53 axis
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044414/
https://www.ncbi.nlm.nih.gov/pubmed/32154226
http://dx.doi.org/10.3389/fbioe.2020.00075
work_keys_str_mv AT wanghaiyong mir29c3psuppressesthemigrationinvasionandcellcycleinesophagealcarcinomaviaccna2p53axis
AT fulinhai mir29c3psuppressesthemigrationinvasionandcellcycleinesophagealcarcinomaviaccna2p53axis
AT weidesheng mir29c3psuppressesthemigrationinvasionandcellcycleinesophagealcarcinomaviaccna2p53axis
AT wangbin mir29c3psuppressesthemigrationinvasionandcellcycleinesophagealcarcinomaviaccna2p53axis
AT zhangchu mir29c3psuppressesthemigrationinvasionandcellcycleinesophagealcarcinomaviaccna2p53axis
AT zhuting mir29c3psuppressesthemigrationinvasionandcellcycleinesophagealcarcinomaviaccna2p53axis
AT mazhifeng mir29c3psuppressesthemigrationinvasionandcellcycleinesophagealcarcinomaviaccna2p53axis
AT lizhupeng mir29c3psuppressesthemigrationinvasionandcellcycleinesophagealcarcinomaviaccna2p53axis
AT wuyuanlin mir29c3psuppressesthemigrationinvasionandcellcycleinesophagealcarcinomaviaccna2p53axis
AT yuguangmao mir29c3psuppressesthemigrationinvasionandcellcycleinesophagealcarcinomaviaccna2p53axis