PUMILIO proteins promote colorectal cancer growth via suppressing p21

Yuanyuan Gong, Zukai Liu, Yihang Yuan, Zhenzhen Yang, Jiawei Zhang, Qin Lu, Wei Wang, Chao Fang (), Haifan Lin () and Sanhong Liu ()
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Yuanyuan Gong: ShanghaiTech University
Zukai Liu: ShanghaiTech University
Yihang Yuan: Shanghai Jiao Tong University School of Medicine (SJTU-SM)
Zhenzhen Yang: ShanghaiTech University
Jiawei Zhang: ShanghaiTech University
Qin Lu: Shanghai Jiao Tong University School of Medicine (SJTU-SM)
Wei Wang: ShanghaiTech University
Chao Fang: Shanghai Jiao Tong University School of Medicine (SJTU-SM)
Haifan Lin: Yale University School of Medicine
Sanhong Liu: ShanghaiTech University

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-29309-1

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