APLN promotes the proliferation, migration, and glycolysis of cervical cancer through the PI3K/AKT/mTOR pathway

Qi Wang; Bingyu Wang; Wenjing Zhang; Teng Zhang; Qingqing Liu; Xinlin Jiao; Jinwen Ye; Yiping Hao; Qun Gao; Guangzhen Ma; Chunyan Hao; Baoxia Cui

doi:10.1016/j.abb.2024.109983

APLN promotes the proliferation, migration, and glycolysis of cervical cancer through the PI3K/AKT/mTOR pathway

Arch Biochem Biophys. 2024 May:755:109983. doi: 10.1016/j.abb.2024.109983. Epub 2024 Mar 30.

Authors

Qi Wang¹, Bingyu Wang², Wenjing Zhang³, Teng Zhang³, Qingqing Liu², Xinlin Jiao³, Jinwen Ye², Yiping Hao², Qun Gao⁴, Guangzhen Ma⁵, Chunyan Hao⁶, Baoxia Cui⁷

Affiliations

¹ Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, Shandong, China.
² Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.
³ Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.
⁴ Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao, 266000, Shandong, China.
⁵ Department of Pathology, The Second People's Hospital of Liaocheng, Liaocheng, 252600, Shandong, China.
⁶ Department of Pathology, School of Basic Medical Sciences and Qilu Hospital, Shandong University, Jinan, Shandong Province, PR China. Electronic address: haochy@sdu.edu.cn.
⁷ Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China. Electronic address: cuibaoxia@sdu.edu.cn.

PMID: 38561035
DOI: 10.1016/j.abb.2024.109983

Abstract

Apelin (APLN) is an endogenous ligand of the G protein-coupled receptor APJ (APLNR). APLN has been implicated in the development of multiple tumours. Herein, we determined the effect of APLN on the biological behaviour and underlying mechanisms of cervical cancer. The expression and survival curves of APLN were determined using Gene Expression Profiling Interactive Analysis. The cellular functions of APLN were detected using CCK-8, clone formation, EdU, Transwell assays, flow cytometry, and seahorse metabolic analysis. The underlying mechanisms were elucidated using gene set enrichment analysis and Western blotting. APLN was upregulated in the samples of patients with cervical cancer and is associated with poor prognosis. APLN knockdown decreased the proliferation, migration, and glycolysis of cervical cancer cells. The opposite results were observed when APLN was overexpressed. Mechanistically, we determined that APLN was critical for activating the PI3K/AKT/mTOR pathway via APLNR. APLN receptor inhibitor ML221 reversed the effect of APLN overexpression on cervical cancer cells. Treatment with LY294002, the PI3K inhibitor, drastically reversed the oncological behaviour of APLN-overexpressing C-33A cells. APLN promoted the proliferation, migration, and glycolysis of cervical cancer cells via the PI3K/AKT/mTOR pathway.

Keywords: APLN; Cervical cancer; Glycolysis; Migration; PI3K/AKT/mTOR pathway; Proliferation.