Knockdown of TRIM65 suppressed the proliferation and invasiveness of gastric cancer cells by restricting the ubiquitin degradation of PPM1A

作者全名："Liu, Chang; Sun, Weiping; Yang, Kui; Xia, Boning"

作者地址："[Liu, Chang; Sun, Weiping; Xia, Boning] Chongqing Med Univ, Dept Gastrointestinal Anorectal Surg, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Yang, Kui] Xi An Jiao Tong Univ, Dept Gen Surg, Affiliated Hosp 1, Xi'an 710061, Shaanxi, Peoples R China; [Xia, Boning] Chongqing Med Univ, Dept Gastrointestinal Anorectal Surg, Affiliated Hosp 2, 74 Linjiang Rd, Chongqing, Peoples R China"

通信作者："Xia, BN (通讯作者)，Chongqing Med Univ, Dept Gastrointestinal Anorectal Surg, Affiliated Hosp 2, 74 Linjiang Rd, Chongqing, Peoples R China."

来源：EXPERIMENTAL CELL RESEARCH

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000802171000002

JCR分区：Q3

影响因子：3.7

年份：2022

卷号：416

期号：2

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结束页：　

文献类型：Article

关键词：Gastric cancer; TRIM65; PPM1A; Ubiquitin degradation

摘要："Gastric cancer is a type of serious malignant tumors all around the world. TCGA data showed that the expression of TRIM65 (E3 ubiquitin ligase) was enhanced in the gastric cancer tissues. The role of TRIM65 in the tumorigenesis of gastric cancer remains unclear. In this study, we successfully established TRIM65-knockdown gastric cancer cells. Next, CCK-8, colony formation assays and transwell assays were performed to detect the cell proliferation and invasion. The results showed that suppression of TRIM65 inhibited the proliferation and invasion of gastric cancer cells. Interestingly, the Western blot assay confirmed that downregulation of TRIM65 increased the level of PPM1A and decreased the level of p-TBK1 in gastric cancer cells. Mechanistically, immunoprecipitation assay revealed that knockdown of TRIM65 inhibited the ubiquitin degradation of PPM1A. In rescue experiments, suppression of PPM1A promoted the proliferation and invasion of gastric cancer cells transfected with sh-TRIM65. Therefore, our results suggested that knockdown of TRIM65 inhibited the proliferation and invasion of gastric cancer cells by suppressing the ubiquitin degradation of PPM1A and phosphorylation of TBK1."

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