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Clinical Significance and Oncogenic Activity of GRWD1 Overexpression in the Development of Colon Carcinoma

Authors Zhou X, Shang J, Liu X, Zhuang JF, Yang YF, Zhang YY, Guan GX

Received 11 November 2020

Accepted for publication 26 January 2021

Published 2 March 2021 Volume 2021:14 Pages 1565—1580

DOI https://doi.org/10.2147/OTT.S290475

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Takuya Aoki


Xin Zhou,1,* Jin Shang,2,* Xing Liu,1,* Jin-Fu Zhuang,1 Yuan-Feng Yang,1 Yi-Yi Zhang,1 Guo-Xian Guan1

1Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, People’s Republic of China; 2The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen, 361102, Fujian, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Guo-Xian Guan
Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, Fujian, People’s Republic of China
Tel +8613609592321
Email [email protected]

Objective: 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.
Materials and Methods: 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.
Results: 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.
Conclusion: 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.

Keywords: proliferation, cell cycle, drug susceptibility, migration and invasion, GRWD1, colon carcinoma

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