Study on the Potential Mechanism of miR-22-5p in Non-Small-Cell Lung Cancer

Abstract

Objective: Non-small-cell lung cancer (NSCLC) ranks among one of the most lethal malignancies worldwide. A better and comprehensive understanding of the mechanism of its malignant progression will be helpful for clinical treating NSCLC.

Methods: The miRNA expression profiles and target gene profiles downloaded from the Gene Expression Omnibus and TargetScan databases were used to identify the key regulatory pattern in NSCLC by bioinformatic analysis. The regulation of miRNA to target mRNA was verified by luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. A series of the in vitro and in vivo experiments were conducted to examine the mechanism of the overexpression or knockdown of the miRNA and/or target gene.

Results: In this study, miR-22-5p was remarkably downregulated in NSCLC than in normal lung cells. The in vitro experiments showed that it could substantially inhibit NSCLC cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) progression. The results of luciferase reporter assay, qRT-PCR, and Western blot revealed that TWIST2 was a direct target gene of miR-22-5p. The results of in vitro and in vivo feedback experiments further demonstrated that miR-22-5p relied on TWIST2-induced malignant progression to regulate NSCLC proliferation, metastasis, and EMT progression.

Conclusions: This study revealed that miR-22-5p downregulation contributed to the malignant progression of NSCLC by targeting TWIST2. The findings highlight a potential novel pathway that could be therapeutically targeted in treating NSCLC.