Zhou Xin, Shang Jin, Liu Xing, Zhuang Jin-Fu, Yang Yuan-Feng, Zhang Yi-Yi, Guan Guo-Xian
Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, People's Republic of China.
The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen, 361102, Fujian, People's Republic of China.
Onco Targets Ther. 2021 Mar 2;14:1565-1580. doi: 10.2147/OTT.S290475. eCollection 2021.
GRWD1 (glutamate-rich WD40 repeat containing 1) is a multifunctional protein involved in multiple cellular regulatory pathways, particularly those associated with cell growth control. GRWD1 is represented as a potential oncogene in several cancers, however, the function and mechanism of GRWD1 in the development of colon cancer are still unknown.
IHC was used to detect the expression of GRWD1 in colon carcinoma tissues. CCK-8, colony formation, and EdU were used to measure the cell proliferation after GRWD1 knockdown and overexpression. The distribution of the cell cycle was analyzed by flow cytometry. The effect of GRWD1 knockdown on migration and invasion was analyzed by wound healing and transwell assays.
Overexpression of GRWD1 in colon carcinoma tissues was associated with pathological grading, tumor size, N stage, TNM stage, and poor survival. GRWD1 had high sensitivity and specificity in distinguishing colon cancer from noncancerous tissues, and might be served as an independent prognosis in colon carcinoma patients. Knockdown of GRWD1 significantly inhibited the cell proliferation and colony formation, and induced cell cycle arrest and more drug susceptibility, and suppressed the migration and invasion. GRWD1 exhibited these oncogenic activities might be associated with its regulation on the expression of PCNA and Ki67, Cyclin A2 and Cyclin B1, ABCC1 and GSTP1, MTA1 and MTA2.
GRWD1 may play an oncogenic activity in the development of colon carcinoma and its overexpression was associated with malignant characteristics and poor survival outcome of colon carcinoma. GRWD1 might be a potential target for future therapy.
富含谷氨酸的WD40重复序列包含蛋白1（GRWD1）是一种多功能蛋白，参与多种细胞调节途径，特别是那些与细胞生长控制相关的途径。GRWD1在几种癌症中被认为是一种潜在的癌基因，然而，GRWD1在结肠癌发生发展中的功能和机制仍不清楚。
采用免疫组化法检测GRWD1在结肠癌组织中的表达。采用CCK-8、集落形成和EdU法检测GRWD1敲低和过表达后的细胞增殖情况。通过流式细胞术分析细胞周期分布。采用伤口愈合试验和Transwell试验分析GRWD1敲低对迁移和侵袭的影响。
GRWD1在结肠癌组织中的过表达与病理分级、肿瘤大小、N分期、TNM分期及不良生存相关。GRWD1在区分结肠癌与非癌组织方面具有较高的敏感性和特异性，可能作为结肠癌患者的独立预后指标。敲低GRWD1可显著抑制细胞增殖和集落形成，诱导细胞周期阻滞和增加药物敏感性，并抑制迁移和侵袭。GRWD1表现出的这些致癌活性可能与其对增殖细胞核抗原（PCNA）和Ki67、细胞周期蛋白A2和细胞周期蛋白B1、ATP结合盒转运蛋白C1（ABCC1）和谷胱甘肽S-转移酶P1（GSTP1）、转移相关蛋白1（MTA1）和转移相关蛋白2（MTA2）表达的调节有关。
GRWD1可能在结肠癌发生发展中发挥致癌活性，其过表达与结肠癌的恶性特征和不良生存结局相关。GRWD1可能是未来治疗的潜在靶点。
