MiR-130a regulates macrophage polarization and is associated with non-small cell lung cancer

Abstract

Lung cancer is the most common cancer as well as the leading cause of cancer-related mortalities worldwide. Macrophages are the most abundant immune cells in primary and metastatic tumors, and contribute to tumor initiation, progression and metastasis. Macrophages have been shown to demonstrate a high level of plasticity, with the ability to undergo dynamic transition between M1 and M2 polarized phenotypes. In the present study, we investigated a pivotal role of miR-130a in macrophage polarization and whether it was associated with poor prognosis in non-small cell lung cancer (NSCLC), using RT-qPCR and western blot analyses. The in vitro experiments showed that miRNA-130a was expressed at a higher level in M1 compared to M2 macrophages. The enforced expression of miR-130a in macrophages resulted in a significantly increased production of proinflammatory cytokines, whereas deletion of miR-130a impaired the M2-associated gene expression and led to an M1-biased response. Mechanistically, the bioinformatics analysis revealed that proliferator-activated receptor γ (PPARγ) is a potential target of miR-130a. Additionally, the luciferase assay confirmed that PPARγ translation was suppressed by miR-130a through the interaction with the 3'UTR of PPARγ mRNA. A subsequent analysis revaled that the induction of miR-130a suppressed PPARγ protein expression. In NSCLC patients, the results showed that miR-130a downregulation exhibited clinical relevance as it was correlated with poor prognosis and increased tumor stage and metastasis. In addition, miR-130a was inversely correlated with the macrophage marker, CD163, and target gene, PPARγ. Taken together, the results established miR-130a as a molecular switch during macrophage development and as a potential target for the treatment of NSCLC.