MicroRNA-508-3p regulates the proliferation of human lung cancer cells by targeting G1 to S phase transition 1 (GSPT1) protein

Xingyou Chen; Chen Feng; Jiliang Zha; Zihao Shen; Wei Ji

doi:10.18388/abp.2020_6660

Xingyou Chen School of Medicine, Nantong University, Nantong, Jiangsu, 226007, China
Chen Feng Department of Thoracic Surgery, The Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, 226001, China
Jiliang Zha Department of Thoracic Surgery, The Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, 226001, China
Zihao Shen Department of Thoracic Surgery, The Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, 226001, China
Wei Ji Department of Thoracic Surgery, Rudong People’s Hospital, Nantong, Jiangsu, 226499, China https://orcid.org/0009-0004-1663-7150

DOI: https://doi.org/10.18388/abp.2020_6660

Abstract

Purpose: Due to its crucial cancer regulatory role, microRNA-508-3p has been reported as a potential therapeutic anticancer molecular target. The present work encompassed the molecular characterization of microRNA-508-3p in lung cancer emphasizing on understanding the possible mechanism of its regulatory action. Methods: qRT-PCR was performed to estimate the relative gene expression of microRNA-508-p in the tissue samples. The proliferation of cancer cells was determined by cell counting kit-8. The colony formation from cancer cells was analyzed by clonogenic assay. Mitotic phase distribution was understood by employing the flow cytometric technique. Edu-Hoechst staining was used for the assessment of cell viability. In silico analysis and dual-luciferase assay were used for target identification of microRNA-508-3p in lung cancer. Immunofluorescence and western blotting studies were carried out for relative protein expression. The rat models were used for performing the in vivo experimental procedures. Results: The study showed the significant down-regulation of microRNA-508-3p in lung cancer. The lower expression levels of microRNA-508-3p were shown to be associated with poor survival of lung cancer patients. The over-expression of microRNA-508-3p was found to decline the proliferation and viability of cancer cells together with the induction of mitotic cell cycle arrest at G1 by targeting G1 to S phase transition 1 (GSPT1) protein. MicroRNA-508-3p up-regulation inhibited the in vivo tumor growth in rat models. Conclusion: Our study identifies miR-508-3p as a pivotal regulator of lung cancer cell proliferation by targeting the GSPT1 protein. This highlights its potential as a tumor suppressor and a therapeutic target for lung cancer. Our findings offer mechanistic insights into miRNA-mediated cancer progression, prompting further research in this intricate regulatory network.