Abstract
Lung cancer is a major health challenge worldwide. Gefitinib, a tyrosine kinase inhibitor (TKI), is the common therapeutic drug used in advanced non-small-cell lung cancer (NSCLC). However, it is eventually bound to face the problem of acquired drug resistance. In this work, we investigated the role of lncRNA MITA1 in the acquisition of gefitinib resistance in NSCLC and uncovered the possible underlying molecular mechanism of the same. Experiments were carried out using the HCC827 and HCC827GR cells. These were transfected with pcDNA-MITA1 or si-MITA1 and treated with gefitinib. Subsequently, lncRNA MITA1 mediated effect on cell viability and apoptosis were studied using the MTT and flow cytometry assays. Furthermore, using qRT-PCR, Western blotting, and immunofluorescence assays, the regulatory association between lncRNA MITA1 and markers of autophagy (LC3, Beclin-1, and p62) were examined by estimating their cellular protein levels. Also, these results were verified in the presence of an autophagy inhibitor bafilomycin A1. We found that MITA1 was highly upregulated in the gefitinib-resistant NSCLC cells, indicating the regulatory role of MITA1 in gefitinib resistance. Mechanistically, upregulated MITA1 led to gefitinib resistance by suppressing apoptosis, increasing cell viability, and inducing autophagy. Furthermore, these results were true when tested in the presence of bafilomycin A1. Our results suggest that MITA1 by inducing autophagy could be a key regulator of gefitinib resistance in NSCLC.