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MUC3A promotes the progression of colorectal cancer through the PI3K/Akt/mTOR pathway

Mucin 3A (MUC3A) is overexpressed in colorectal cancer (CRC) and associated with poor prognosis, but the related mechanism remains unclear. Our study found that MUC3A promotes the progression of CRC by activating the PI3K/Akt/mTOR signaling pathway. Knockout of MUC3A significantly inhibited the prol...

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Autores principales: Su, Wei, Feng, Baijie, Hu, Lina, Guo, Xianzhi, Yu, Minghua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161576/
https://www.ncbi.nlm.nih.gov/pubmed/35655161
http://dx.doi.org/10.1186/s12885-022-09709-8
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author Su, Wei
Feng, Baijie
Hu, Lina
Guo, Xianzhi
Yu, Minghua
author_facet Su, Wei
Feng, Baijie
Hu, Lina
Guo, Xianzhi
Yu, Minghua
author_sort Su, Wei
collection PubMed
description Mucin 3A (MUC3A) is overexpressed in colorectal cancer (CRC) and associated with poor prognosis, but the related mechanism remains unclear. Our study found that MUC3A promotes the progression of CRC by activating the PI3K/Akt/mTOR signaling pathway. Knockout of MUC3A significantly inhibited the proliferation of CRC cells and induced G1 phase arrest by upregulating p21 protein, an important cell cycle regulator. Moreover, knockout of MUC3A significantly inhibited invasion ability and enhanced the sensitivity to the chemotherapeutic agent 5-FU. Furthermore, we found that knockout of MUC3A repressed the PI3K/Akt/mTOR pathway through RNA-seq. Treatment with the PI3K/Akt/mTOR pathway inhibitor rapamycin successfully eliminated the difference in proliferation, invasion and chemoresistance between MUC3A knockout cells and control cells. Our study suggests that MUC3A is a potential oncogene that promotes the proliferation, invasion, and chemotherapy resistance of CRC. Moreover, CRC patients with high expression of MUC3A may benefit from rapamycin treatment.  SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09709-8.
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spelling pubmed-91615762022-06-03 MUC3A promotes the progression of colorectal cancer through the PI3K/Akt/mTOR pathway Su, Wei Feng, Baijie Hu, Lina Guo, Xianzhi Yu, Minghua BMC Cancer Research Mucin 3A (MUC3A) is overexpressed in colorectal cancer (CRC) and associated with poor prognosis, but the related mechanism remains unclear. Our study found that MUC3A promotes the progression of CRC by activating the PI3K/Akt/mTOR signaling pathway. Knockout of MUC3A significantly inhibited the proliferation of CRC cells and induced G1 phase arrest by upregulating p21 protein, an important cell cycle regulator. Moreover, knockout of MUC3A significantly inhibited invasion ability and enhanced the sensitivity to the chemotherapeutic agent 5-FU. Furthermore, we found that knockout of MUC3A repressed the PI3K/Akt/mTOR pathway through RNA-seq. Treatment with the PI3K/Akt/mTOR pathway inhibitor rapamycin successfully eliminated the difference in proliferation, invasion and chemoresistance between MUC3A knockout cells and control cells. Our study suggests that MUC3A is a potential oncogene that promotes the proliferation, invasion, and chemotherapy resistance of CRC. Moreover, CRC patients with high expression of MUC3A may benefit from rapamycin treatment.  SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09709-8. BioMed Central 2022-06-02 /pmc/articles/PMC9161576/ /pubmed/35655161 http://dx.doi.org/10.1186/s12885-022-09709-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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
Su, Wei
Feng, Baijie
Hu, Lina
Guo, Xianzhi
Yu, Minghua
MUC3A promotes the progression of colorectal cancer through the PI3K/Akt/mTOR pathway
title MUC3A promotes the progression of colorectal cancer through the PI3K/Akt/mTOR pathway
title_full MUC3A promotes the progression of colorectal cancer through the PI3K/Akt/mTOR pathway
title_fullStr MUC3A promotes the progression of colorectal cancer through the PI3K/Akt/mTOR pathway
title_full_unstemmed MUC3A promotes the progression of colorectal cancer through the PI3K/Akt/mTOR pathway
title_short MUC3A promotes the progression of colorectal cancer through the PI3K/Akt/mTOR pathway
title_sort muc3a promotes the progression of colorectal cancer through the pi3k/akt/mtor pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161576/
https://www.ncbi.nlm.nih.gov/pubmed/35655161
http://dx.doi.org/10.1186/s12885-022-09709-8
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