@article{27a7fe32642a4352a550577f0812a604,
title = "Increased co-expression of PSMA2 and GLP-1 receptor in cervical cancer models in type 2 diabetes attenuated by Exendin-4: A translational case-control study",
abstract = "Background: Type 2 diabetes (T2D) increases the risk of many types of cancer. Dysregulation of proteasome-related protein degradation leads to tumorigenesis, while Exendin-4, a glucagon-like peptide 1 receptor (GLP-1R) agonist, possesses anti-cancer effects. Methods: We explored the co-expression of proteasome alpha 2 subunit (PSMA2) and GLP-1R in the Cancer Genome Atlas (TCGA) database and human cervical cancer specimens, supplemented by in vivo and in vitro studies using multiple cervical cancer cell lines. Findings: PSMA2 expression was increased in 12 cancer types in TCGA database and cervical cancer specimens from patients with T2D (T2D vs non-T2D: 3.22 (95% confidence interval CI: 1.38, 5.05) vs 1.00 (0.66, 1.34) fold change, P = 0.01). psma2-shRNA decreased cell proliferation in vitro, and tumour volume and Ki67 expression in vivo. Exendin-4 decreased psma2 expression, tumour volume and Ki67 expression in vivo. There was no change in GLP-1R expression in 12 cancer types in TCGA database. However, GLP-1R expression (T2D vs non-T2D: 5.49 (3.0, 8.1) vs 1.00 (0.5, 1.5) fold change, P < 0.001) was increased and positively correlated with PSMA2 expression in T2D-related (r = 0.68) but not in non-T2D-related cervical cancer specimens. This correlation was corroborated by in vitro experiments where silencing glp-1r decreased psma2 expression. Exendin-4 attenuated phospho-p65 and -IκB expression in the NF-κB pathway. Interpretation: PSMA2 and GLP-1R expression in T2D-related cervical cancer specimens was increased and positively correlated, suggesting hyperglycaemia might promote cancer growth by increasing PSMA2 expression which could be attenuated by Exendin-4.",
keywords = "Cancer, Exendin-4, GLP-1R, PSMA, Type 2 diabetes",
author = "Dandan Mao and Huanyi Cao and Mai Shi and Wang, {Chi Chiu} and Joseph Kwong and Li, {Joshua Jing Xi} and Yong Hou and Xing Ming and Lee, {Heung Man} and Tian, {Xiao Yu} and Wong, {Chun Kwok} and Elaine Chow and Kong, {Alice Pik Shan} and Lui, {Vivian Wai Yan} and Chan, {Paul Kay Sheung} and Chan, {Juliana Chung Ngor}",
note = "Funding Information: JCNC reported receiving research grants and/or honoraria for consultancy or giving lectures from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Pfizer, and Sanofi. EC reported receiving grants from Lee Powder and Sanofi. VWYL received a University-Industry Collaboration Program (UIM/329; from the Innovation and Technology Fund, Hong Kong government, and Lee's Pharmaceutical [Hong Kong Limited] in 2018–2020) and served as a scientific consultant for Novartis Pharmaceutical (Hong Kong) Limited (Oct 2015–Oct 2016). Funding Information: VWYL is funded by the General Research Fund (# 17121616 , # 14168517 ), Research Impact Fund (# R4017-18 ) from Research Grant Council, Hong Kong; the Health and Medical Research Fund (HMRF # 15160691 , the Health and Medical Research Fund, the Food and Health Bureau, the Government of the Hong Kong SAR), University-Industry Collaboration Program (UIM/329; Innovation and Technology Fund, Hong Kong government), and the Hong Kong Cancer Fund. Funding Information: This project was supported by the CUHK Postdoctoral Fellowship Scheme. CUHK Direct Grant and CUHK Diabetes Research and Education Fund of the Department of Medicine and Therapeutics, Faculty of Medicine, CUHK. VWYL is funded by the General Research Fund (#17121616, #14168517), Research Impact Fund (#R4017-18) from Research Grant Council, Hong Kong; the Health and Medical Research Fund (HMRF #15160691, the Health and Medical Research Fund, the Food and Health Bureau, the Government of the Hong Kong SAR), University-Industry Collaboration Program (UIM/329; Innovation and Technology Fund, Hong Kong government), and the Hong Kong Cancer Fund. Funding Information: This project was supported by the CUHK Postdoctoral Fellowship Scheme. CUHK Direct Grant and CUHK Diabetes Research and Education Fund of the Department of Medicine and Therapeutics, Faculty of Medicine, CUHK. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = mar,
doi = "10.1016/j.ebiom.2021.103242",
language = "English (US)",
volume = "65",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",
}