Dual role and ceRNA networks of miR-146a in lung cancer: regulating proliferation, metastasis, and chemoresistance

Abstract

Lung cancer persists as the predominant cause of cancer-related mortality globally. MicroRNAs, a class of short non-coding RNAs, are recognized as critical regulators in the pathogenesis of lung cancer, functioning either as oncogenes or tumor suppressors. Among these, miR-146a has been identified as a significant modulator in non-small-cell lung cancer, exerting influence over cellular proliferation, resistance to chemotherapy, apoptosis, and metastatic potential. Notably, miR-146a displays a dualistic role, acting as either a tumor suppressor or an oncogene depending on the molecular mechanisms. Furthermore, its interaction with non-coding RNAs—including circular and long non-coding RNAs—through a competing endogenous RNA network contributes additional regulatory complexity. Dysregulation of miR-146a–associated ceRNA networks influences tumor proliferation, invasion, immune evasion, and therapy resistance. Despite the breadth of existing research, the mechanisms underlying this dual behavior remain insufficiently clarified. This review synthesizes current findings regarding miR-146a’s bidirectional functions and explores its potential clinical applications as both a diagnostic marker and a therapeutic target in lung cancer.