GNAS-AS1/miR-4319/NECAB3 axis promotes migration and invasion of non-small cell lung cancer cells by altering macrophage polarization

Abstract

Non-small cell lung cancer (NSCLC) represents for approximately 85% of all lung cancers, which is the most common cancer worldwide. Tumor-associated macrophages (TAM) are crucial for tumor progression, which was widely believed to be mediated by long non-coding RNAs (LncRNAs). We aimed to explore the effect of one LncRNA, GNAS-AS1, in TAM-associated NSCLC progression. Relative mRNA levels were determined by qRT-PCR. Western blot and ELISA were used to detect protein levels. Proliferation in vitro was assessed by MTT and clone formation assays. Migration and invasion of cell lines were evaluated by transwell-based assays. Interaction between molecules was detected by luciferase report assay. GNAS-AS1 expression was dramatically enhanced in TAM, NSCLC cell lines, and clinical tumor tissues, and negatively correlated with overall survival of NSCLC patients. GNAS-AS1 promoted macrophage M2 polarization and NSCLC cell progression via directly inhibiting miR-4319, which could target N-terminal EF-hand calcium binding protein 3 (NECAB3) to inhibit its expression. GNAS-AS1/miR-4319/NECAB3 axis promotes tumor progression of NSCLC by altering macrophage polarization. This novel mechanism may provide potential strategy for NSCLC treatment.