Hsa-miR-548k blocks the drug resistance cascade in NSCLC cancer by targeting the key genes involved in various chemotherapy resistance pathways

Abstract

Although new therapeutic approaches have been developed, and efforts have been made to understand cancer signaling pathways, drug resistance remains the most common cause of tumor recurrence and therapy. microRNAs degrade mRNAs or target their specific sequences as translation repressors. miRNA disruption may alter the drug sensitivity of cancer cells and influence tumor cell resistance to chemotherapy. Modulation of miRNAs through antagomiRs or mimics inhibit tumor cell proliferation and enhance drug sensitivity by regulating critical gene networks and signaling pathways. miRNAs that simultaneously involve the 3′-UTR of genes responsible for various drug resistance pathways in lung cancer were identified with the miRvestigator algorithm. Its validity was confirmed with TargetScan and the expression level of introduced genes was investigated under the influence of its mimic. Finally, the percentage of viable cells was determined using the apoptosis assay. Hsa-miR-548k was identified as a potential gene regulator of multiple drug resistance signaling in lung cancer using miRvestigator bioinformatics algorithms. Hsa-miR-548k mimics were transiently transfected into A549 cells to investigate the effect of hsa-miR-548k on the expression of ATP-binding cassette super-family G member 2 (ABCG2), epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), Yes1 Associated Transcriptional Regulator (YAP), and vascular endothelial growth factor (VEGF). Quantitative analyses confirmed significant downregulation of the gene expression levels involved in lung cancer drug resistance pathways by hsa-miR-548k. Furthermore, hsa-miR-548k overexpression increased the apoptosis of A549 cells. This study not only confirmed the significance of hsa-miR-548k in regulating drug resistance pathways but also identified it as a new target for the treatment of lung cancer.