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MEX3A promotes the malignant progression of ovarian cancer by regulating intron retention in TIMELESS

The latest research shows that RNA-binding proteins (RBPs) could serve as novel potential targets for cancer therapy. We used bioinformatics analysis to screen and identify the key RBPs in ovarian cancer, from which we found that Mex-3 RNA Binding Family Member A (MEX3A) was intimately associated wi...

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Autores principales: Li, Fangfang, Zhao, Chen, Diao, Yuchao, Wang, Zixiang, Peng, Jiali, Yang, Ning, Qiu, Chunping, Kong, Beihua, Li, Yingwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205863/
https://www.ncbi.nlm.nih.gov/pubmed/35715407
http://dx.doi.org/10.1038/s41419-022-05000-7
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author Li, Fangfang
Zhao, Chen
Diao, Yuchao
Wang, Zixiang
Peng, Jiali
Yang, Ning
Qiu, Chunping
Kong, Beihua
Li, Yingwei
author_facet Li, Fangfang
Zhao, Chen
Diao, Yuchao
Wang, Zixiang
Peng, Jiali
Yang, Ning
Qiu, Chunping
Kong, Beihua
Li, Yingwei
author_sort Li, Fangfang
collection PubMed
description The latest research shows that RNA-binding proteins (RBPs) could serve as novel potential targets for cancer therapy. We used bioinformatics analysis to screen and identify the key RBPs in ovarian cancer, from which we found that Mex-3 RNA Binding Family Member A (MEX3A) was intimately associated with the clinical prognosis of ovarian cancer. Nevertheless, little is known about its biological roles in ovarian cancer. In this case, we observed that MEX3A was highly overexpressed in fresh-frozen ovarian cancer tissues. MEX3A knockdown suppressed the development and invasion of ovarian cancer cells, while MEX3A overexpression promoted the proliferation and invasion of ovarian cancer cells. Mechanistically, TIMELESS was the critical downstream target gene of MEX3A, as demonstrated through alternative splicing event analysis based on RNA-seq. MEX3A knockdown resulted in retention of intron twenty-three of TIMELESS mRNA and decreased TIMELESS mRNA owing to stimulation of nonsense-mediated RNA decay (NMD). Additionally, we found that TIMELESS overexpression with MEX3A knockdown partially restored the proliferation ability of ovarian cancer cells. The results of this paper demonstrated that the MEX3A/TIMELESS signaling pathway was a key regulator of ovarian cancer, and MEX3A was a novel possible treatment target for ovarian cancer patients.
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spelling pubmed-92058632022-06-19 MEX3A promotes the malignant progression of ovarian cancer by regulating intron retention in TIMELESS Li, Fangfang Zhao, Chen Diao, Yuchao Wang, Zixiang Peng, Jiali Yang, Ning Qiu, Chunping Kong, Beihua Li, Yingwei Cell Death Dis Article The latest research shows that RNA-binding proteins (RBPs) could serve as novel potential targets for cancer therapy. We used bioinformatics analysis to screen and identify the key RBPs in ovarian cancer, from which we found that Mex-3 RNA Binding Family Member A (MEX3A) was intimately associated with the clinical prognosis of ovarian cancer. Nevertheless, little is known about its biological roles in ovarian cancer. In this case, we observed that MEX3A was highly overexpressed in fresh-frozen ovarian cancer tissues. MEX3A knockdown suppressed the development and invasion of ovarian cancer cells, while MEX3A overexpression promoted the proliferation and invasion of ovarian cancer cells. Mechanistically, TIMELESS was the critical downstream target gene of MEX3A, as demonstrated through alternative splicing event analysis based on RNA-seq. MEX3A knockdown resulted in retention of intron twenty-three of TIMELESS mRNA and decreased TIMELESS mRNA owing to stimulation of nonsense-mediated RNA decay (NMD). Additionally, we found that TIMELESS overexpression with MEX3A knockdown partially restored the proliferation ability of ovarian cancer cells. The results of this paper demonstrated that the MEX3A/TIMELESS signaling pathway was a key regulator of ovarian cancer, and MEX3A was a novel possible treatment target for ovarian cancer patients. Nature Publishing Group UK 2022-06-17 /pmc/articles/PMC9205863/ /pubmed/35715407 http://dx.doi.org/10.1038/s41419-022-05000-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Li, Fangfang
Zhao, Chen
Diao, Yuchao
Wang, Zixiang
Peng, Jiali
Yang, Ning
Qiu, Chunping
Kong, Beihua
Li, Yingwei
MEX3A promotes the malignant progression of ovarian cancer by regulating intron retention in TIMELESS
title MEX3A promotes the malignant progression of ovarian cancer by regulating intron retention in TIMELESS
title_full MEX3A promotes the malignant progression of ovarian cancer by regulating intron retention in TIMELESS
title_fullStr MEX3A promotes the malignant progression of ovarian cancer by regulating intron retention in TIMELESS
title_full_unstemmed MEX3A promotes the malignant progression of ovarian cancer by regulating intron retention in TIMELESS
title_short MEX3A promotes the malignant progression of ovarian cancer by regulating intron retention in TIMELESS
title_sort mex3a promotes the malignant progression of ovarian cancer by regulating intron retention in timeless
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205863/
https://www.ncbi.nlm.nih.gov/pubmed/35715407
http://dx.doi.org/10.1038/s41419-022-05000-7
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