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
Publication in refereed journal

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其它資訊
摘要Background: Type 2 diabetes (T2D) increases the risk of many types of cancer. Dysregulation of proteasomerelated 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 -IkB expression in the NF-kB 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.
出版社接受日期28.01.2021
著者Dandan Mao, Huanyi Cao, Mai Shi, Chi Chiu Wang, Joseph Kwong, Joshua Jing Xi Li, Yong Hou, Xing Ming, Heung Man Lee, Xiao Yu Tian, Chun Kwok Wong, Elaine Chow, Alice Pik Shan Kong, Vivian Wai Yan Lui, Paul Kay Sheung Chan, Juliana Chung Ngor Chan
期刊名稱EBioMedicine
出版年份2021
月份3
卷號65
出版社Elsevier
文章號碼103242
國際標準期刊號2352-3964
電子國際標準期刊號2352-3964
語言英式英語
關鍵詞Type 2 diabetes, Cancer, Exendin-4, PSMA, GLP-1R

上次更新時間 2021-11-10 於 23:59