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Updated: May 15, 2026

Using Nicotine in a Silica-Exposed Mouse Model to Promote Lung Epithelial-Mesenchymal Transition
Published on: March 3, 2023
Nicotine promotes cell proliferation through α5-nAChR/RRM2 axis in lung adenocarcinoma
Jingting Wang1, Jingtan Li2, Qiang Li1
1Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, Shandong, China.
Abstract:
Alpha 5 nicotinic acetylcholine receptor (α5-nAChR) is involved in nicotine-induced lung adenocarcinoma (LUAD) cell proliferation. Ribonucleotide Reductase Subunit M2 (RRM2) plays an important role in the development of LUAD and resistance to chemotherapy drugs. Cyclin-dependent kinase 1 (CDK1) is a potential downstream effector of RRM2. Notably, our gene expression profile shows that α5-nAChR was positively correlated with the expression of RRM2 and CDK1. However, little is known about the link between α5-nAChR and RRM2 in nicotine-related LUAD. Here, we identified a link between α5-nAChR and RRM2 in LUAD. α5-nAChR expression was associated with RRM2 expression, smoking status, and poor prognosis. In vitro experiments demonstrated that α5-nAChR mediates nicotine-induced CDK1, RRM2 expression via STAT3, thereby enhancing LUAD cell proliferation and migration. Furthermore, the functional link among α5-nAChR, RRM2, and CDK1 was confirmed both in mouse xenograft tissues and human LUAD tissues. These findings uncover a novel role of α5-nAChR/RRM2 axis involved in nicotine-related LUAD progression.
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