Ubiquitin-Like Protein UBD Promotes Cell Proliferation in Colorectal Cancer by Facilitating p53 Degradation

作者全名："Su, Hongbin; Qin, Mengdi; Liu, Qiang; Jin, Bo; Shi, Xianjun; Xiang, Zheng"

作者地址："[Su, Hongbin; Qin, Mengdi; Liu, Qiang; Jin, Bo; Shi, Xianjun; Xiang, Zheng] Chongqing Med Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Chongqing, Peoples R China; [Su, Hongbin; Qin, Mengdi; Liu, Qiang; Xiang, Zheng] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Dept Gen Surg, Chongqing, Peoples R China"

通信作者："Xiang, Z (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Chongqing, Peoples R China.; Xiang, Z (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Dept Gen Surg, Chongqing, Peoples R China."

来源：FRONTIERS IN ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000680651600001

JCR分区：Q2

影响因子：4.7

年份：2021

卷号：11

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：colorectal cancer; UBD; p53; proliferation; degradation

摘要："Purpose Ubiquitin D (UBD) is a member of the ubiquitin-like modifier (UBL) family and is highly expressed in a variety of cancers including colorectal cancer (CRC). However, the mechanisms of its regulatory roles in CRC are largely elusive. In this study, we revealed the effect of UBD on the proliferation of CRC. Methods The expression of UBD in clinical tissue samples of CRC and seven CRC cell lines was detected using qRT-PCR, immunohistochemistry (IHC) and Western blotting. CCK-8, colony formation, EdU and flow cytometry assays were used to detect the functional changes of CRC cells transfected with UBD stable expression plasmids in vitro. A xenograft model was constructed to assess the effect of UBD on the growth of CRC cells in vivo. The connection between UBD and p53 was analyzed using Western blotting, immunoprecipitation, proteasome inhibition assay and Cycloheximide (CHX) chase assay. Results UBD was overexpressed in CRC tumor tissues compared with nontumor tissues, and its overexpression was positively associated with the tumor size and TNM stage of CRC patients. Functionally, UBD significantly accelerated CRC cell viability and proliferation in vitro and promoted tumorigenesis in vivo. Mechanistically, UBD interacted with p53 in CRC cells, downregulated the expression of p53 by regulating its degradation, shortened the p53 half-life, thereby further affecting the decrease in p21 and the increase in Cyclin D1, Cyclin E, CDK2, CDK4 and CDK6. Moreover, in vivo experiments showed that UBD-induced tumor growth in nude mice was dependent on a decrease in p53. Conclusions Our study proved that UBD mediates the degradation of p53, thereby facilitating the growth of CRC cells and ultimately promoting the progression of CRC. Therefore, UBD may be a potential therapeutic target and a promising prognostic biomarker for CRC."

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