Promotive role of USP29-mediated deubiquitination in malignant proliferation of colorectal cancer cells via the KIAA1429/SOX8 axis

作者全名："Li, Juncai; Yang, Jianguo; Chen, Zhenzhou; Liu, Li; Wang, Hao; Deng, Qican; Chen, Yajun; Que, Yong; Fu, Zhongxue"

作者地址："[Li, Juncai; Yang, Jianguo; Deng, Qican; Fu, Zhongxue] Chongqing Med Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Chongqing, Peoples R China; [Li, Juncai; Liu, Li] Peoples Hosp Yubei Dist Chongqing City, Dept Surg, Chongqing, Peoples R China; [Chen, Zhenzhou; Wang, Hao; Chen, Yajun; Fu, Zhongxue] Chongqing Med Univ, Affiliated Hosp 3, Chongqing, Peoples R China; [Wang, Hao] Chengdu Med Coll, Affiliated Hosp 1, Dept Surg, Chengdu, Peoples R China; [Que, Yong] Peoples Hosp Chongqing Hechuan, Dept Gastroenterol, Chongqing, Peoples R China"

通信作者："Fu, ZX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Chongqing, Peoples R China.; Fu, ZX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 3, Chongqing, Peoples R China."

来源：BIOMOLECULES AND BIOMEDICINE

ESI学科分类：　

WOS号：WOS:000989925500012

JCR分区：　

影响因子：　

年份：2023

卷号：23

期号：3

开始页：483

结束页：495

文献类型：Article

关键词：Colorectal cancer (CRC); ubiquitin-specific peptidases 29 (USP29); KIAA1429; SRY-box transcription factor 8 (SOX8); TPD52; malignant proliferation

摘要："Colorectal cancer (CRC) is regarded as one of the most prevalent neoplasms worldwide, and ubiquitination and N6-methyladenosine (m6A) modification regulate the outgrowth of multiple cancers. This study attempted to explore the effect of ubiquitin-specific peptidases 29 (USP29) on the malignant proliferation of CRC cells via stabilizing Vir-like m6A methyltransferase associated (VIRMA/KIAA1429). First, upregulations of USP29, KIAA1429, and SRY-box transcription factor 8 (SOX8) were found in CRC tissues and cells through real-time quantitative polymerase chain reaction and Western blotting. After transfection of si-USP29, the proliferation of CRC cells was evaluated by the cell counting kit-8, colony formation, and 5-ethynyl-2'-deoxyuridine assays, and we observed that depletion of USP29 inhibited the proliferation of CRC cells. Co-immunoprecipitation confirmed the binding of USP29 to KIAA1429. Mechanically, USP29 mediated deubiquitination to stabilize the protein levels of KIAA1429, and KIAA1429 promoted the stability of SOX8 mRNA through m6A modification. Moreover, overexpression of KIAA1429 or SOX8 reversed the inhibitory effects of USP29 depletion on CRC cell proliferation. Finally, the xenograft tumor model revealed the promotive role of USP29 in the proliferation of CRC cells in vivo. Altogether, USP29 facilitates the malignant proliferation of CRC cells via upregulating the KIAA1429/SOX8 axis."

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