HOTAIR induces EGFR-TKIs resistance in non-small cell lung cancer through epithelial-mesenchymal transition

•Down-regulation of HOTAIR was associated with EGFR-TKIs resistance.•HOTAIR may enhance activation of apoptosis and EMT.•HOTAIR overexpression restored gefitinib sensitivity in EGFR-TKI resistant cell lines.•HOTAIR expression was associated with primary and acquired resistance to EGFR-TKIs.•HOTAIR might be able to act as a biomarker to predict the EGFR-TKIs resistance. Previous research found that HOTAIR, a long non-coding RNA, is aberrantly expressed and associated with tumor invasion, metastasis and chemo-resistance in many cancers. The aim of this study was to investigate the role of HOTAIR in resistance of EGFR-TKIs in NSCLC. HOTAIR expression level was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in NSCLC cell lines or tumor tissues. A total of 62 samples with EGFR-mutant and EGFR-TKI-sensitive NSCLCs, 42 with acquired resistance and 27 with primary resistance to EGFR-TKIs were analyzed. The effect of HOTAIR on cell proliferation and apoptosis was undergone by CCK-8 and flow cytometry assays. The expression of EMT proteins was assessed by western blot. HOTAIR was significantly down-regulated in lung cancer cells (PC9/R, H1975, H1299 and A549) and patients with primary and acquired resistance to EGFR-TKIs. In clinical setting, high levels of HOTAIR expression was significantly correlated with longer progression-free survival (PFS) [P