Epigenetic silencing of miR-483-3p promotes acquired gefitinib resistance and EMT in EGFR-mutant NSCLC by targeting integrin β3

• DOI: 10.1038/s41388-018-0276-2
• Publication Date: 2018-04-30T10:26:45Z
• Authors: Jinnan Yue; Dacheng Lv; Caiyun Wang; Ling Li; Qingnan Zhao; Hongzhuan Chen; Lu Xu
• Keywords: Male; Mice, Inbred BALB C; 0303 health sciences; Epithelial-Mesenchymal Transition; Lung Neoplasms; Integrin beta3; Mice, Nude; Gefitinib; Article; Epigenesis, Genetic; 3. Good health; ErbB Receptors; Mice; MicroRNAs; 03 medical and health sciences; Drug Resistance, Neoplasm; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Animals; Humans; Gene Silencing; Apoptosis Regulatory Proteins; Protein Kinase Inhibitors; Cell Proliferation

All lung cancers patients with epidermal growth factor receptor (EGFR) mutation inevitably develop acquired resistance to EGFR tyrosine kinase inhibitors (TKI). In up 30% of cases, the mechanism underlying remains unknown. MicroRNAs (miRNAs) is a group small non-coding RNAs commonly dysregulated in human and have been implicated therapy resistance. The aim this study was understand roles novel miRNAs TKI EGFR-mutant non-small cell cancer (NSCLC). Here, we reported evidence miR-483-3p silencing epithelial-to-mesenchymal transition (EMT) phenotype both vitro vivo NSCLC models gefitinib. those tumor models, forced expression efficiently increased sensitivity gefitinib-resistant cells gefitinib by inhibiting proliferation promoting apoptosis. Moreover, reversed EMT inhibited migration, invasion, metastasis cells. Mechanistically, directly targeted integrin β3, thus repressed downstream FAK/Erk signaling pathway. Furthermore, due hypermethylation its own promoter. Taken together, our data identify as promising target for combination overcome NSCLC.