miR-1246 enhances chemo-resistance of polyploid giant cancer cells in H1299 cells by targeting GSK3β/β-catenin.

Non-small cell lung cancer (NSCLC) is characterized by a high mortality rate. Chemotherapy has been observed to potentially increase the prevalence of polyploid giant cancer cells (PGCCs), which may play a role in the development of chemo-resistance in NSCLC. The dysregulated expression of miR-1246 has been implicated in the modulation of gene expression related to drug resistance. Therefore, the objective of this study is to examine the role of miRNA-1246 in PGCCs and to elucidate its regulatory mechanisms. H1299 cells were treated with 100 nM docetaxel (Doc) for 24 h, then allowed to recover for 3 days to form polyploid giant cancer cells (PGCCs). The miRNA profiles of these PGCCs were analyzed, focusing on miR-1246. Transfection with miR-1246 mimics or inhibitors was performed, and various assays were used to assess the effects of miR-1246 inn PGCCs. The study found miR-1246 levels were significantly higher in PGCCs than in the original cells, affecting chemo-resistance, apoptosis, migration, and epithelial-mesenchymal transition. These findings suggested that NSCLC H1299 cells may employ polyploidy formation as a survival mechanism in response to docetaxel-based treatment, mediated by the miR-1246/GSK3β/β-catenin axis, ultimately leading to enhanced chemo-resistance.