文献类型：期刊文献

英文题名：Ribosome assembly factor URB1 contributes to colorectal cancer proliferation through transcriptional activation of ATF4

作者：Wang, Tao[1,2];Li, Lai-Yuan[1];Chen, Yi-Feng[1];Fu, Si-Wu[3];Wu, Zhi-Wei[4];Du, Bin-Bin[1];Yang, Xiong-Fei[1];Zhang, Wei-Sheng[1];Hao, Xiang-Yong[5];Guo, Tian-Kang[2,5]

第一作者：Wang, Tao

通信作者：Hao, XY[1];Guo, TK[1]

机构：[1]Gansu Prov Peoples Hosp, Dept Colorectal Surg, Lanzhou, Peoples R China;[2]Lanzhou Univ, Sch Clin Med 1, Lanzhou, Peoples R China;[3]Northwest Minzu Univ, Sch Med Coll, Lanzhou, Peoples R China;[4]Gansu Univ Tradit Chinese Med, Sch Preclin Med, Lanzhou, Peoples R China;[5]Gansu Prov Peoples Hosp, Dept Gen Surg, 204 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China

第一机构：Gansu Prov Peoples Hosp, Dept Colorectal Surg, Lanzhou, Peoples R China

通信机构：[1]corresponding author), Gansu Prov Peoples Hosp, Dept Gen Surg, 204 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China.

年份：2021

卷号：112

期号：1

起止页码：101

外文期刊名：CANCER SCIENCE

收录：;Scopus(收录号：2-s2.0-85097006648);WOS:【SCI-EXPANDED(收录号:WOS:000596009200001)】；

基金：National Natural Science Foundation of China, Grant/Award Number: 81660157; Gansu Provincial Health Committee, Grant/Award Number: GSWSKY-2019-69; Gansu Provincial Nature Science Foundation for Young Scientists & Technology Planning Project, Grant/Award Number: 18JR3RA058; Gansu Provincial People's Hospital, Grant/Award Numbers: 19SYPYB-6, 19SYPYB-7, 18GSSY42, 18GSSY3-1.

语种：英文

外文关键词：ATF4; colorectal cancer; cyclin A2; ribosome assembly factor; URB1; XBP1

摘要：Ribosome assembly factor URB1 is essential for ribosome biogenesis. However, its latent role in cancer remains unclear. Analysis of The Cancer Genome Atlas database and clinical tissue microarray staining showed that URB1 expression was upregulated in colorectal cancer (CRC) and prominently related to clinicopathological characteristics. Silencing of URB1 hampered human CRC cell proliferation and growth in vitro and in vivo. Microarray screening, ingenuity pathway analysis, and JASPAR assessment indicated that activating transcription factor 4 (ATF4) and X-box binding protein 1 (XBP1) are potential downstream targets of URB1 and could transcriptionally interact through direct binding. Silencing of URB1 significantly decreased ATF4 and cyclin A2 (CCNA2) expression in vivo and in vitro. Restoration of ATF4 effectively reversed the malignant proliferation phenotype of URB1-silenced CRC cells. Dual-luciferase reporter and ChIP assays indicated that XBP1 transcriptionally activated ATF4 by binding with its promoter region. X-box binding protein 1 colocalized with ATF4 in the nuclei of RKO cells, and ATF4 mRNA expression was positively regulated by XBP1. This study shows that URB1 contributes to oncogenesis and CRC growth through XBP1-mediated transcriptional activation of ATF4. Therefore, URB1 could be a potential therapeutic target for CRC.