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
Processing time: 210 Days and 3.8 Hours
ARTICLE HIGHLIGHTS
Research background

Colorectal cancer (CRC) is one of the most prevalent and deadly types of cancer worldwide. Despite advances in treatment options, the molecular mechanisms underlying CRC development and progression are not fully understood. Recently, dopamine and cyclic adenosine monophosphate (cAMP)-regulated phosphoprotein with an apparent Mr of 32000 (DARPP-32) has emerged as a potential player in CRC. DARPP-32 is known for its involvement in dopamine and cAMP signaling pathways in the brain, but its role in CRC remains largely unexplored. Understanding the function and molecular mechanisms of DARPP-32 in CRC could provide valuable insights into the pathogenesis of this disease and potentially uncover new therapeutic targets.

Research motivation

CRC is a significant health concern, and understanding the underlying molecular mechanisms driving its progression is crucial for developing effective treatments. The role of DARPP-32, a protein involved in dopamine and cAMP signaling, in CRC remains poorly understood. Investigating the function of DARPP-32 in CRC could reveal its potential as a therapeutic target and shed light on novel pathways involved in tumor development and progression.

Research objectives

We aimed to enhance our understanding of the involvement of DARPP-32 in CRC progression and potentially identify novel therapeutic targets for the treatment of this disease.

Research methods

Since the effect of DARPP-32 on colorectal neoplasia is unknown, this study combined bioinformatics analysis, quantitative polymerase chain reaction, western blotting, tissue microarrays, and a variety of in vitro and in vivo functional tests to investigate this effect.

Research results

We found that DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC. Overexpression of DARPP-32 was shown to promote cancer progression. DARPP-32 knockdown resulted in the opposite functional effect. Mechanistically, DARPP-32 may regulate the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway to carry out its biological function.

Research conclusions

The collective results demonstrate that DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway.

Research perspectives

Further investigation is needed to reveal the precise molecular mechanisms through which DARPP-32 regulates the PI3K/AKT signaling pathway in CRC. Identifying the specific downstream targets and upstream regulators of DARPP-32 will provide a deeper understanding of its role in cancer progression.