A microRNA‑125a variant, which affects its mature processing, increases the risk of radiation‑induced pneumonitis in patients with non‑small‑cell lung cancer.

Abstract

The present study aimed to investigate the role of microRNA (miR)‑125a in the development of pneumonitis inpatients with non‑small‑cell lung cancer that received radiotherapy. In addition, the study aimed to determine how the miR‑125a affects its target, transforming growth factor β (TGFβ). Bioinformatics tools were used to identify a potential miR‑125a binding site in the 3'untranslated region of TGFβ, which was subsequently confirmed using a dual‑luciferase reporter system. In addition, tissue samples were collected from patients with lung cancer and genotyped as CC (n=36), CT (n=28) or TT (n=6). The expression levels of miR‑125a and TGFβ in these samples were determined, and CC genotype samples demonstrated upregulated miR‑125a expression, and downregulated TGFβ protein and mRNA expression compared with samples carrying the minor allele, T. To further investigate the association between the rs12976445 polymorphism and the risk of pneumonitis in patients with lung cancer that received radiotherapy, 534 lung cancer patients diagnosed with pneumonitis and 489lung cancer patients without pneumonitis were recruited. rs12976445 was shown to be significantly associated with the risk of pneumonitis. In conclusion, the rs12976445 polymorphism increased expression levels of TGFβ by decreasing the expression of miR‑125a, and therefore may be associated with the development of pneumonitis in patients with lung cancer that receive radiotherapy.