Upregulation of MicroRNA-146a Increases the Sensitivity of Cisplatin-Resistant Lung Cancer Cells to Chemotherapy Through the Toll-Like Receptor-Signaling Pathway

Background and Objective: Cisplatin, a platinum-based chemical, is a key agent in cancer treatment but is often associated with the development of resistance in several cancers. This resistance has been linked to miRNAs, which play crucial roles in gene regulation. In this study, the involvement of miRNAs in cisplatin resistance in NSCLC cells was explored. Materials and Methods: The differentially expressed miRNAs (DEMs) identified using the GSE43249 dataset and various bioinformatics tools. The experimental part involved culturing A549 cells, inducing cisplatin resistance, transfecting cells with miR-146a and assessing gene expression changes. Statistical analysis of the data was performed using R software and GraphPad Prism to elucidate the underlying mechanisms of drug resistance. Results: The downregulation of specific miRNAs, especially miR-146a. Functional studies revealed that miR-146a could target the TLR signaling pathway, a crucial pathway in cellular response. Notably, transfection with a miR-146a mimic increased the sensitivity of resistant cells to cisplatin, signifying a potential therapeutic avenue. Further, miR-146a was shown to downregulate the expression of key genes like TNF, MYD88 and IRAK1 in the resistant cells. Conclusion: This study provides insights into the molecular mechanisms behind cisplatin resistance in NSCLC cells and suggests potential therapeutic strategies leveraging miRNA modulation.