ARL4C Regulates the Progression of Clear Cell Renal Cell Carcinoma by Affecting the Wnt/beta-Catenin Signaling Pathway

作者全名："Zhang, Peizhi; Xu, Yingkun; Chen, Shaoan; Wang, Zicheng; Zhao, Leizuo; Chen, Chen; Kang, Weiting; Han, Rongyu; Qiu, Jiechuan; Wang, Qingliang; Gao, Han; Wu, Guangzhen; Xia, Qinghua"

作者地址："[Zhang, Peizhi; Chen, Shaoan; Zhao, Leizuo; Chen, Chen; Kang, Weiting; Xia, Qinghua] Shandong Univ, Shandong Prov Hosp, Cheeloo Coll Med, Dept Urol, Jinan 250021, Peoples R China; [Xu, Yingkun] Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrine & Breast Surg, Chongqing 400042, Peoples R China; [Wang, Zicheng; Han, Rongyu; Qiu, Jiechuan; Wang, Qingliang; Gao, Han] Shandong First Med Univ, Shandong Prov Hosp, Dept Urol, Jinan 250021, Peoples R China; [Zhao, Leizuo] Dongying Peoples Hosp, Dept Urol, Dongying 257000, Peoples R China; [Chen, Chen] Shandong Univ, Liaocheng Peoples Hosp, Dept Urol, Liaocheng 252000, Peoples R China; [Wu, Guangzhen] Dalian Med Univ, Affiliated Hosp 1, Dept Urol, Dalian 116011, Liaoning, Peoples R China"

通信作者："Xia, QH (通讯作者)，Shandong Univ, Shandong Prov Hosp, Cheeloo Coll Med, Dept Urol, Jinan 250021, Peoples R China."

来源：JOURNAL OF ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000820933100002

JCR分区：Q2

影响因子：4.501

年份：2022

卷号：2022

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Purpose. To investigate the expression of the ADP-ribosylation factor (ARF)-like proteins (ARLs) and ARL4C in clear cell renal cell carcinoma (ccRCC) based on bioinformatics analysis and experimentally determine the effect and mechanism of ARL4C on cellular properties involved in ccRCC progression. Methods. After downloading the data of cancer patients from the TCGA database, we used various bioinformatics analysis websites and methods to analyze the expression and function of ARLs and ARL4C. The differential expression of ARL4C in clinical renal cancer tissues versus adjacent normal tissues was further verified using immunohistochemistry and real-time quantitative reverse-transcription (qRT-PCR). qRT-PCR was used to explore the expression of ARL4C mRNA in normal renal cells versus different ccRCC cell lines, and the protein expression of ARL4C was further verified using western blotting. CCK-8, colony formation, and EdU assays were used to determine the effect of ARL4C knockdown on ccRCC cell proliferation. We also used wound healing and Transwell assays to analyze the changes in ccRCC cell migration and invasion following ARL4C knockdown. Finally, we used western blotting to probe the molecular mode of action of ARL4C in ccRCC cells after exposure to Wnt signaling pathway agonists. Results. Biological function analysis showed that methylation of ARL4C and changes in immune cell infiltration and targeted drug sensitivity caused by altered ARL4C expression affected the prognosis of ccRCC. Further bioinformatics analysis suggested that the expression of ARL4C mRNA was increased in ccRCC, and this was associated with a poor prognosis in ccRCC patients. Increased expression of ARL4C was further verified using qRT-PCR and western blotting of human ccRCC tissue samples. Downregulation of ARL4C significantly inhibited the proliferation, migration, and invasion of ccRCC cells, and activation of the Wnt/beta-catenin pathway promoted the expression of ARL4C. As an essential downstream effector of the Wnt signaling pathway, ARL4C increased the expression of cyclin D1 and c-myc, thereby increasing the ability of the cells to undergo epithelial-mesenchymal transition (EMT) and ccRCC progression. Conclusions. As a critical factor in the Wnt/beta-catenin pathway, ARL4C regulates EMT and progression in ccRCC."

基金机构："National Natural Science Foundation of China [82072816, 81672553]"

基金资助正文："AcknowledgmentsThis work was supported by the National Natural Science Foundation of China (Grant nos. 82072816 and 81672553). In addition, Peizhi Zhang thanked Yanjie Wang for her guidance and contribution to this experiment."