Dysregulated expression of microRNA involved in resistance to osimertinib in EGFR mutant non-small cell lung cancer cells

Abstract

Background: An increasing amount of evidence has confirmed that the altered expression of microRNAs (miRNAs) is critical to the mechanism underlying primary and even acquired resistance to tyrosine kinase inhibitors (TKIs). However, studies on the linkage between the altered miRNAs expression and osimertinib resistance are few, and the effect of miRNAs in this context is still unclear. In the light of this, we hypothesized that the differential expression of multiple miRNAs is the driver in the osimertinib resistance process. Thus, the aim of our study was to find differentially expressed miRNAs in non-small cell lung cancer cells resistant to osimertinib.Methods: An AZD9291(Osimertinib)-resistant cell line model was constructed, and the differential miRNAs between epidermal growth factor receptor (EGFR)-sensitive cell lines A549 and H1975 and the corresponding drug-resistant cell lines were identified via biosynthesis analysis.Results: In the A549 osimertinib-resistant cell line, 93 miRNAs were upregulated and 94 miRNAs were downregulated. In the H1975 osimertinib-resistant cell line, 124 miRNAs were upregulated and 53 miRNAs were downregulated. Finally, 7 significantly different miRNAs were screened using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.Conclusions: This study on the mechanism of target therapy in lung cancer systematically and comprehensively examined the miRNAs involved in osimertinib resistance. It was found that miR- 708-5p, miR-708-3p, miR-10395-3p, miR-7704 miR-34a-5p, miR-19b-1-5p, and miR-219a-5p may play key roles in osimertinib resistance.

Unraveling the Role of MicroRNAs: Potential Biomarkers for Gestational Diabetes Mellitus Revealed Through RNA Sequencing Analysis

“…In a previous study, it inferred that miR-6734-5p might be a significant miRNA associated with high-grade serous ovarian cancer [36]. miR-10395-3p was poorly studied, and currently, its dysregulation has only been supposed to play significant role in lung cancer [37]. Unfortunately, in GDM even diabetes models, these miRNAs have not been reported to have relevant effects.…”

Human Metapneumovirus-Induced Host microRNA Expression Impairs the Interferon Response in Macrophages and Epithelial Cells

“…The overexpression of hsa-miR-1913 was also associated with multiple forms of cancer [44][45][46][47][48][49], similar to hsa-miR-7704 [50][51][52]. However, the role of these miRNAs in HMPV infection warrants additional research.…”