PUMILIO proteins promote colorectal cancer growth via suppressing p21

PUMILIO (PUM) proteins belong to the highly conserved PUF family post-transcriptional regulators involved in diverse biological processes. However, their function in carcinogenesis remains under-explored. Here, we report that Pum1 and Pum2 display increased expression in human colorectal cancer (CRC...

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Autores principales: Gong, Yuanyuan, Liu, Zukai, Yuan, Yihang, Yang, Zhenzhen, Zhang, Jiawei, Lu, Qin, Wang, Wei, Fang, Chao, Lin, Haifan, Liu, Sanhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956581/
https://www.ncbi.nlm.nih.gov/pubmed/35338151
http://dx.doi.org/10.1038/s41467-022-29309-1
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author Gong, Yuanyuan
Liu, Zukai
Yuan, Yihang
Yang, Zhenzhen
Zhang, Jiawei
Lu, Qin
Wang, Wei
Fang, Chao
Lin, Haifan
Liu, Sanhong
author_facet Gong, Yuanyuan
Liu, Zukai
Yuan, Yihang
Yang, Zhenzhen
Zhang, Jiawei
Lu, Qin
Wang, Wei
Fang, Chao
Lin, Haifan
Liu, Sanhong
author_sort Gong, Yuanyuan
collection PubMed
description PUMILIO (PUM) proteins belong to the highly conserved PUF family post-transcriptional regulators involved in diverse biological processes. However, their function in carcinogenesis remains under-explored. Here, we report that Pum1 and Pum2 display increased expression in human colorectal cancer (CRC). Intestine-specific knockout of Pum1 and Pum2 in mice significantly inhibits the progression of colitis-associated cancer in the AOM/DSS model. Knockout or knockdown of Pum1 and/or Pum2 in human CRC cells result in a significant decrease in the tumorigenicity and delayed G1/S transition. We identify p21/Cdkn1a as a direct target of PUM1. Abrogation of the PUM1 binding site in the p21 mRNA also results in decreased cancer cell growth and delayed G1/S transition. Furthermore, intravenous injection of nanoparticle-encapsulated anti-Pum1 and Pum2 siRNAs reduces colorectal tumor growth in murine orthotopic colon cancer models. These findings reveal the requirement of PUM proteins for CRC progression and their potential as therapeutic targets.
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spelling pubmed-89565812022-04-20 PUMILIO proteins promote colorectal cancer growth via suppressing p21 Gong, Yuanyuan Liu, Zukai Yuan, Yihang Yang, Zhenzhen Zhang, Jiawei Lu, Qin Wang, Wei Fang, Chao Lin, Haifan Liu, Sanhong Nat Commun Article PUMILIO (PUM) proteins belong to the highly conserved PUF family post-transcriptional regulators involved in diverse biological processes. However, their function in carcinogenesis remains under-explored. Here, we report that Pum1 and Pum2 display increased expression in human colorectal cancer (CRC). Intestine-specific knockout of Pum1 and Pum2 in mice significantly inhibits the progression of colitis-associated cancer in the AOM/DSS model. Knockout or knockdown of Pum1 and/or Pum2 in human CRC cells result in a significant decrease in the tumorigenicity and delayed G1/S transition. We identify p21/Cdkn1a as a direct target of PUM1. Abrogation of the PUM1 binding site in the p21 mRNA also results in decreased cancer cell growth and delayed G1/S transition. Furthermore, intravenous injection of nanoparticle-encapsulated anti-Pum1 and Pum2 siRNAs reduces colorectal tumor growth in murine orthotopic colon cancer models. These findings reveal the requirement of PUM proteins for CRC progression and their potential as therapeutic targets. Nature Publishing Group UK 2022-03-25 /pmc/articles/PMC8956581/ /pubmed/35338151 http://dx.doi.org/10.1038/s41467-022-29309-1 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
Gong, Yuanyuan
Liu, Zukai
Yuan, Yihang
Yang, Zhenzhen
Zhang, Jiawei
Lu, Qin
Wang, Wei
Fang, Chao
Lin, Haifan
Liu, Sanhong
PUMILIO proteins promote colorectal cancer growth via suppressing p21
title PUMILIO proteins promote colorectal cancer growth via suppressing p21
title_full PUMILIO proteins promote colorectal cancer growth via suppressing p21
title_fullStr PUMILIO proteins promote colorectal cancer growth via suppressing p21
title_full_unstemmed PUMILIO proteins promote colorectal cancer growth via suppressing p21
title_short PUMILIO proteins promote colorectal cancer growth via suppressing p21
title_sort pumilio proteins promote colorectal cancer growth via suppressing p21
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956581/
https://www.ncbi.nlm.nih.gov/pubmed/35338151
http://dx.doi.org/10.1038/s41467-022-29309-1
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