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m(6)A methyltransferase KIAA1429 acts as an oncogenic factor in colorectal cancer by regulating SIRT1 in an m(6)A-dependent manner

N6-methyladenosine (m6A) modifications of RNAs are involved in various aspects of colorectal carcinogenesis via regulation of mRNA stability, splicing, and translation. KIAA1429, an m6A methyltransferase, was found deregulated in multiple cancer types. However, its role in colorectal cancer remains...

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Autores principales: Zhou, Yuan, Pei, Zhengda, Maimaiti, Aizezi, Zheng, Linyi, Zhu, Zhongcheng, Tian, Mengxiang, Zhou, Zhongyi, Tan, Fengbo, Pei, Qian, Li, Yuqiang, Liu, Wenxue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8881457/
https://www.ncbi.nlm.nih.gov/pubmed/35217651
http://dx.doi.org/10.1038/s41420-022-00878-w
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author Zhou, Yuan
Pei, Zhengda
Maimaiti, Aizezi
Zheng, Linyi
Zhu, Zhongcheng
Tian, Mengxiang
Zhou, Zhongyi
Tan, Fengbo
Pei, Qian
Li, Yuqiang
Liu, Wenxue
author_facet Zhou, Yuan
Pei, Zhengda
Maimaiti, Aizezi
Zheng, Linyi
Zhu, Zhongcheng
Tian, Mengxiang
Zhou, Zhongyi
Tan, Fengbo
Pei, Qian
Li, Yuqiang
Liu, Wenxue
author_sort Zhou, Yuan
collection PubMed
description N6-methyladenosine (m6A) modifications of RNAs are involved in various aspects of colorectal carcinogenesis via regulation of mRNA stability, splicing, and translation. KIAA1429, an m6A methyltransferase, was found deregulated in multiple cancer types. However, its role in colorectal cancer remains elusive. By analyzing TCGA and GEPIA database, we found that KIAA1429 in colorectal cancer was highly expressed. In addition, we used immunohistochemistry, western blotting, and QRT-PCR to detect the expression of KIAA1429 in colorectal cancer samples and cell lines, and we found that KIAA1429 was overexpressed in colorectal cancer sample and cell line. Functionally, silencing of KIAA1429 by shRNA in colorectal cancer cell lines resulted in decreased cell proliferation, colony formation, and migration. On the contrary, overexpression of KIAA1429 increased cell proliferation, colony formation, and migration. Further mechanism analysis demonstrated that KIAA1429 increased the expression of SIRT1 via regulating its mRNA stability in an m6A-dependent manner. More importantly, in vivo experiment showed that depletion of KIAA1429 significantly inhibited colorectal tumor growth. In conclusion, our results suggested that the m6A methyltransferase KIAA1429 promotes the growth and motility of colorectal cancer and could be a potent therapeutic target.
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spelling pubmed-88814572022-03-17 m(6)A methyltransferase KIAA1429 acts as an oncogenic factor in colorectal cancer by regulating SIRT1 in an m(6)A-dependent manner Zhou, Yuan Pei, Zhengda Maimaiti, Aizezi Zheng, Linyi Zhu, Zhongcheng Tian, Mengxiang Zhou, Zhongyi Tan, Fengbo Pei, Qian Li, Yuqiang Liu, Wenxue Cell Death Discov Article N6-methyladenosine (m6A) modifications of RNAs are involved in various aspects of colorectal carcinogenesis via regulation of mRNA stability, splicing, and translation. KIAA1429, an m6A methyltransferase, was found deregulated in multiple cancer types. However, its role in colorectal cancer remains elusive. By analyzing TCGA and GEPIA database, we found that KIAA1429 in colorectal cancer was highly expressed. In addition, we used immunohistochemistry, western blotting, and QRT-PCR to detect the expression of KIAA1429 in colorectal cancer samples and cell lines, and we found that KIAA1429 was overexpressed in colorectal cancer sample and cell line. Functionally, silencing of KIAA1429 by shRNA in colorectal cancer cell lines resulted in decreased cell proliferation, colony formation, and migration. On the contrary, overexpression of KIAA1429 increased cell proliferation, colony formation, and migration. Further mechanism analysis demonstrated that KIAA1429 increased the expression of SIRT1 via regulating its mRNA stability in an m6A-dependent manner. More importantly, in vivo experiment showed that depletion of KIAA1429 significantly inhibited colorectal tumor growth. In conclusion, our results suggested that the m6A methyltransferase KIAA1429 promotes the growth and motility of colorectal cancer and could be a potent therapeutic target. Nature Publishing Group UK 2022-02-25 /pmc/articles/PMC8881457/ /pubmed/35217651 http://dx.doi.org/10.1038/s41420-022-00878-w 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
Zhou, Yuan
Pei, Zhengda
Maimaiti, Aizezi
Zheng, Linyi
Zhu, Zhongcheng
Tian, Mengxiang
Zhou, Zhongyi
Tan, Fengbo
Pei, Qian
Li, Yuqiang
Liu, Wenxue
m(6)A methyltransferase KIAA1429 acts as an oncogenic factor in colorectal cancer by regulating SIRT1 in an m(6)A-dependent manner
title m(6)A methyltransferase KIAA1429 acts as an oncogenic factor in colorectal cancer by regulating SIRT1 in an m(6)A-dependent manner
title_full m(6)A methyltransferase KIAA1429 acts as an oncogenic factor in colorectal cancer by regulating SIRT1 in an m(6)A-dependent manner
title_fullStr m(6)A methyltransferase KIAA1429 acts as an oncogenic factor in colorectal cancer by regulating SIRT1 in an m(6)A-dependent manner
title_full_unstemmed m(6)A methyltransferase KIAA1429 acts as an oncogenic factor in colorectal cancer by regulating SIRT1 in an m(6)A-dependent manner
title_short m(6)A methyltransferase KIAA1429 acts as an oncogenic factor in colorectal cancer by regulating SIRT1 in an m(6)A-dependent manner
title_sort m(6)a methyltransferase kiaa1429 acts as an oncogenic factor in colorectal cancer by regulating sirt1 in an m(6)a-dependent manner
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8881457/
https://www.ncbi.nlm.nih.gov/pubmed/35217651
http://dx.doi.org/10.1038/s41420-022-00878-w
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