PUMILIO proteins promote colorectal cancer growth via suppressing p21

被引：35

作者：

Gong, Yuanyuan ^{[1
,2
,3
,4
]}

Liu, Zukai ^{[1
,2
]}

Yuan, Yihang ^{[5
,6
]}

Yang, Zhenzhen ^{[1
,2
]}

Zhang, Jiawei ^{[1
,2
]}

Lu, Qin ^{[5
,6
]}

Wang, Wei ^{[1
,2
]}

Fang, Chao ^{[5
,6
,7
,8
]}

Lin, Haifan ^{[9
,10
]}

Liu, Sanhong ^{[1
,2
,11
]}

机构：

[1] ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China

[2] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China

[3] Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Shanghai, Peoples R China

[4] Univ Chinese Acad Sci, Beijing, Peoples R China

[5] Shanghai Jiao Tong Univ, Sch Med SJTU SM, Hongqiao Int Inst Med, Tongren Hosp, Shanghai, Peoples R China

[6] Shanghai Jiao Tong Univ, Sch Med SJTU SM, Dept Pharmacol & Chem Biol, State Key Lab Oncogenes & Related Genes, Shanghai, Peoples R China

[7] Zunyi Med Univ, Minist Educ, Key Lab Basic Pharmacol, Zunyi, Guizhou, Peoples R China

[8] Zunyi Med Univ, Minist Educ, Joint Int Res Lab Ethnomed, Zunyi, Guizhou, Peoples R China

[9] Yale Univ, Sch Med, Yale Stem Cell Ctr, New Haven, CT 06520 USA

[10] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA

[11] Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai Frontiers Sci Ctr TCM Chem Biol, Shanghai, Peoples R China

来源：

NATURE COMMUNICATIONS | 2022年 / 13卷 / 01期

基金：

中国国家自然科学基金;

关键词：

RNA-BINDING PROTEINS; STEM-CELLS; TUMOR-SUPPRESSOR; LIVER METASTASES; COLON; GENE; PUM1; REVEALS; FAMILY; IDENTIFICATION;

D O I：

10.1038/s41467-022-29309-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

RNA binding proteins can contribute to colorectal cancer (CRC) initiation and development. Here the authors show that PUMILIO proteins, PUM1 and PUM2 contribute to CRC growth by inhibiting p21 expression. 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.

引用

页数：17

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