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YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells

RNA methylation can reverse the methylation modification at the RNA level, which is an extremely important epigenetic modification. The function and mechanism of YTHDF2, as a reader of m6A modification, in epithelial ovarian cancer (EOC) have not been elucidated so far. This study aimed to investiga...

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Autores principales: Li, Jie, Wu, Lei, Pei, Meili, Zhang, Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501604/
https://www.ncbi.nlm.nih.gov/pubmed/32948220
http://dx.doi.org/10.1186/s13048-020-00717-5
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author Li, Jie
Wu, Lei
Pei, Meili
Zhang, Yun
author_facet Li, Jie
Wu, Lei
Pei, Meili
Zhang, Yun
author_sort Li, Jie
collection PubMed
description RNA methylation can reverse the methylation modification at the RNA level, which is an extremely important epigenetic modification. The function and mechanism of YTHDF2, as a reader of m6A modification, in epithelial ovarian cancer (EOC) have not been elucidated so far. This study aimed to investigate how YTHDF2 and miR-145 modulated EOC progression through m6A modification. It demonstrated that YTHDF2 was significantly upregulated in EOC tissues compared with normal ovarian tissues. Further functional studies confirmed that YTHDF2 significantly promoted the proliferation and migration of EOC cell lines and reduced the global 6-methyladenine (m6A) mRNA levels. Next, the expression levels of miR-145 and YTHDF2 were found to be inversely correlated in ovarian cancer tissues and cells, and YTHDF2 was the direct target gene of miR-145. A crucial crosstalk occurred between miR-145 and YTHDF2 via a double-negative feedback loop. The overexpression of YTHDF2 rescued miR-145-induced reduction of the proliferation and migration of EOC cells. Hence, YTHDF2 and miR-145, as two crucial m6A regulators, were involved in the progression of EOC by indirectly modulating m6A levels. The findings of this study on YTHDF2 and miR-145 might provide new insights into carcinogenesis and new potential therapeutic targets for EOC.
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spelling pubmed-75016042020-09-22 YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells Li, Jie Wu, Lei Pei, Meili Zhang, Yun J Ovarian Res Research RNA methylation can reverse the methylation modification at the RNA level, which is an extremely important epigenetic modification. The function and mechanism of YTHDF2, as a reader of m6A modification, in epithelial ovarian cancer (EOC) have not been elucidated so far. This study aimed to investigate how YTHDF2 and miR-145 modulated EOC progression through m6A modification. It demonstrated that YTHDF2 was significantly upregulated in EOC tissues compared with normal ovarian tissues. Further functional studies confirmed that YTHDF2 significantly promoted the proliferation and migration of EOC cell lines and reduced the global 6-methyladenine (m6A) mRNA levels. Next, the expression levels of miR-145 and YTHDF2 were found to be inversely correlated in ovarian cancer tissues and cells, and YTHDF2 was the direct target gene of miR-145. A crucial crosstalk occurred between miR-145 and YTHDF2 via a double-negative feedback loop. The overexpression of YTHDF2 rescued miR-145-induced reduction of the proliferation and migration of EOC cells. Hence, YTHDF2 and miR-145, as two crucial m6A regulators, were involved in the progression of EOC by indirectly modulating m6A levels. The findings of this study on YTHDF2 and miR-145 might provide new insights into carcinogenesis and new potential therapeutic targets for EOC. BioMed Central 2020-09-18 /pmc/articles/PMC7501604/ /pubmed/32948220 http://dx.doi.org/10.1186/s13048-020-00717-5 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Li, Jie
Wu, Lei
Pei, Meili
Zhang, Yun
YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells
title YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells
title_full YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells
title_fullStr YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells
title_full_unstemmed YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells
title_short YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells
title_sort ythdf2, a protein repressed by mir-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501604/
https://www.ncbi.nlm.nih.gov/pubmed/32948220
http://dx.doi.org/10.1186/s13048-020-00717-5
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