Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2023; 15(11): 1936-1950
Published online Nov 15, 2023. doi: 10.4251/wjgo.v15.i11.1936
Dopamine and cyclic adenosine monophosphate-regulated phosphoprotein with an apparent Mr of 32000 promotes colorectal cancer growth
Kuan He, Chao-Zheng Xie, Ya Li, Zhen-Zhou Chen, Shi-Hao Xu, Si-Qi Huang, Jian-Guo Yang, Zheng-Qiang Wei, Xu-Dong Peng
Kuan He, Chao-Zheng Xie, Ya Li, Shi-Hao Xu, Si-Qi Huang, Jian-Guo Yang, Zheng-Qiang Wei, Xu-Dong Peng, Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400000, China
Zhen-Zhou Chen, Gastrointestinal Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 400000, China
Author contributions: He K conceived and designed the study; He K, Xie CZ, and Li Y performed the experimental tasks; He K and Chen ZZ collected the data; He K, Xu SH, Huang SQ, and Yang JG analyzed and interpreted the data; He K and Peng XD drafted the article; Wei ZQ and Peng XD critically revised the article; All authors have read and approved the final manuscript.
Supported by Chongqing Key Diseases Research and Application Demonstration Program, No. 2019ZX003; General Project of Chongqing Nature Science Foundation, No. cstc2021jcyj-msxmX0283.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (Chongqing Medical University; Protocol No. IACUC-CQMU-2022-0019, Committee on Management and Use of Laboratory Animals of Chongqing Medical University, Chongqing, China).
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xu-Dong Peng, PhD, Doctor, Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing 400000, China. 846393577@qq.com
Received: April 19, 2023
Peer-review started: April 19, 2023
First decision: June 20, 2023
Revised: June 29, 2023
Accepted: July 29, 2023
Article in press: July 29, 2023
Published online: November 15, 2023
Abstract
BACKGROUND

Dopamine and cyclic adenosine monophosphate (cAMP)-regulated phosphoprotein with an apparent Mr of 32000 (DARPP-32) is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brain. However, recent studies have shown that DARPP-32 is also expressed in other tissues, including colorectal cancer (CRC), where its function is not well understood.

AIM

To explore the effect of DARPP-32 on CRC progression.

METHODS

The expression levels of DARPP-32 were assessed in CRC tissues using both quantitative polymerase chain reaction and immunohistochemistry assays. The proliferative capacity of CRC cell lines was evaluated with Cell Counting Kit-8 and 5-ethynyl-2’-deoxyuridine assays, while apoptosis was measured by flow cytometry. The migratory and invasive potential of CRC cell lines were determined using wound healing and transwell chamber assays. In vivo studies involved monitoring the growth rate of xenograft tumors. Finally, the underlying molecular mechanism of DARPP-32 was investigated through RNA-sequencing and western blot analyses.

RESULTS

DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC. Overexpression of DARPP-32 was shown to promote cancer cell proliferation, migration, and invasion and reduce apoptosis. DARPP-32 knockdown resulted in the opposite functional effects. Mechanistically, DARPP-32 may regulate the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in order to carry out its biological function.

CONCLUSION

DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway.

Keywords: Colorectal cancer, Dopamine and cyclic adenosine monophosphate-regulated phosphoprotein with an apparent Mr of 32000, Proliferation, Migration, Phosphoinositide 3-kinase, Akt

Core Tip: Dopamine and cyclic adenosine monophosphate-regulated phosphoprotein with an apparent Mr of 32000 (DARPP-32) is frequently upregulated in colorectal cancer (CRC). Overexpression of DARPP-32 promoted cancer cell proliferation, migration, and invasion and reduced apoptosis. Mechanistic investigations revealed that DARPP-32 appeared to exert its oncogenic functions through regulation of the phosphoinositide 3-kinase/Akt signaling pathway, which is involved in cell survival and proliferation. These findings indicate that DARPP-32 plays an essential role in facilitating CRC tumorigenesis and progression. Therefore, DARPP-32 may represent a potential novel biomarker and therapeutic target for CRC treatment.