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World J Stem Cells. Jun 26, 2020; 12(6): 481-487
Published online Jun 26, 2020. doi: 10.4252/wjsc.v12.i6.481
Multifaceted p21 in carcinogenesis, stemness of tumor and tumor therapy
Bo-Duan Xiao, Yu-Jia Zhao, Xiao-Yuan Jia, Jiong Wu, Yi-Gang Wang, Fang Huang
Bo-Duan Xiao, Fang Huang, Department of Pathology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
Bo-Duan Xiao, Yu-Jia Zhao, Xiao-Yuan Jia, Jiong Wu, Yi-Gang Wang, Xinyuan Institute of Medicine and Biotechnology, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
Author contributions: Huang F and Wang YG contributed to the conception and design of the paper, literature review, critical revision and approval of the final version; Xiao BD, Zhao YJ, and Wu J searched the literature and wrote the paper; Jia XY drew the picture, and revised the paper.
Supported by the Natural Science Foundation of Zhejiang Province of China, No. LY18C070002 and No. LY16H160056;National Natural Science Foundation of China, No. 81803069;the 521 Talent Project of Zhejiang Sci-Tech University; and Science Foundation of Zhejiang Sci‐Tech University, No. 18042291‐Y.
Conflict-of-interest statement: All other authors have nothing to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Fang Huang, PhD, Assistant Professor, Department of Pathology, Zhejiang Provincial People’s Hospital, 158 Shangtang Road, Hangzhou 310014, Zhejiang Province, China. huangfang0794@163.com
Received: January 15, 2020
Peer-review started: January 15, 2020
First decision: March 16, 2020
Revised: April 7, 2020
Accepted: May 5, 2020
Article in press: May 5, 2020
Published online: June 26, 2020
Processing time: 161 Days and 23.5 Hours
Abstract

Cancer cells possess metabolic properties that are different from those of benign cells. p21, encoded by CDKN1A gene, also named p21Cip1/WAF1, was first identified as a cyclin-dependent kinase regulator that suppresses cell cycle G1/S phase and retinoblastoma protein phosphorylation. CDKN1A (p21) acts as the downstream target gene of TP53 (p53), and its expression is induced by wild-type p53 and it is not associated with mutant p53. p21 has been characterized as a vital regulator that involves multiple cell functions, including G1/S cell cycle progression, cell growth, DNA damage, and cell stemness. In 1994, p21 was found as a tumor suppressor in brain, lung and colon cancer by targeting p53 and was associated with tumorigenesis and metastasis. Notably, p21 plays a significant role in tumor development through p53-dependent and p53-independent pathways. In addition, expression of p21 is closely related to the resting state or terminal differentiation of cells. p21 is also associated with cancer stem cells and acts as a biomarker for such cells. In cancer therapy, given the importance of p21 in regulating the G1/S and G2 check points, it is not surprising that p21 is implicated in response to many cancer treatments and p21 promotes the effect of oncolytic virotherapy.

Keywords: p21; CDKN1A; Tumorigenesis; Circular RNA; Stemness of tumor; Cancer stem cells; Tumor therapy

Core tip: p21, as a cyclin-dependent kinase regulator, suppresses cell cycle G1/S phase and retinoblastoma protein phosphorylation. As the downstream target gene of TP53, p21 expression is induced by wild-type p53. p21 was found as a tumor suppressor in several cancers by targeting p53 and was associated with tumorigenesis and metastasis. Notably, p21 is also associated with cancer stem cells. Moreover, p21 is closely related to cancer therapy, and it can promote antitumor effect of oncolytic virotherapy. These findings implicated multifaceted roles of p21 in cancer treatment.