MiR-320a is associated with cisplatin resistance in lung adenocarcinoma and its clinical value in non-small cell lung cancer: a comprehensive analysis based on microarray data

2020 
Abstract Background Currently, the main therapy for NSCLC is a surgery and chemotherapy. Although great progress has been made in targeted treatment and immunotherapy, the survival rates are still low which is associated with resistance to chemotherapy. Previous studies have shown the histone acetylation and microRNAs(miRNAs) might play an important role in chemotherapy resistance. The aim of this study was to identify candidate miRNA of cisplatin (DDP) resistance in lung adenocarcinoma. Methods We used 5-aza-2′-deoxycytidine and trichostatin A to reversed drug resistance of A549/DDP cells in vitro, and miRNA expression profiling were determined by microarrays to found the candidate miRNAs. In addition, we investigated the correlations between miR-320a expression and clinical characteristics through data collected from Gene Expression Omnibus (GEO) microarrays, The Cancer Genome Atlas (TCGA) to determine the clinical role of miR-320a in lung adenocarcinoma. Furthermore, we investigated the biological function of miR-320a. TargetScanHuman, PicTar2005 and miRanda v5.1. were used to predict the target genes of miR-320a; then the function of those genes would be suggested from those enrichment of GO items and KEGG. Results The treatments of 5-Aza-dc significantly inhibited cellular proliferation, and increased apoptosis of A549/DDP cells compared with untreated cells. TSA did not reverse the cisplatin resistance. MiR-320a was up-regulated in revering the cisplatin resistance. The lung adenocarcinoma groups had a significantly lower level of miR-320a expression than the control groups. As for the bioinformatics analyses, we found some target genes involved in cell cycle progression, tumor progression, MAPK signaling pathway, ErbB signaling pathway. The promising target genes were highly enriched in various pathways in cancer. Conclusions The current study validated that miR-320a was up-regulated in revering the cisplatin resistance. The results of bioinformatics analyses may present a new method for investigating the pathogenesis of lung adenocarcinoma.
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