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

doi:10.4251/wjgo.v15.i11.1936

Dopamine and cyclic adenosine monophosphate-regulated phosphoprotein with an apparent Mr of 32000 promotes colorectal cancer growth

World J Gastrointest Oncol. 2023 Nov 15;15(11):1936-1950. doi: 10.4251/wjgo.v15.i11.1936.

Authors

Kuan He¹, Chao-Zheng Xie¹, Ya Li¹, Zhen-Zhou Chen², Shi-Hao Xu¹, Si-Qi Huang¹, Jian-Guo Yang¹, Zheng-Qiang Wei¹, Xu-Dong Peng³

Affiliations

¹ Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400000, China.
² Gastrointestinal Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 400000, China.
³ Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400000, China. 846393577@qq.com.

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