Qi Wang1, Xuefei Li2, Shengxiang Ren1, Chunxia Su1, Chunyu Li3, Wei Li1, Jia Yu1, Ningning Cheng4, Caicun Zhou5. 1. Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, 200433, PR China. 2. Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, 200433, PR China. 3. Department of Integrated Chinese Traditional and Western Medicine, International Medical School, Tianjin Medical University, Tianjin, 300070, PR China. 4. Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, PR China. Electronic address: ningcnn@163.com. 5. Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, 200433, PR China. Electronic address: caicunzhoudr@163.com.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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 < 0.01] compared with low HOTAIR expression subgroup in tumors which respond to EGFR-TKIs. In vitro, over-expression HOTAIR could restore gefitinib sensitivity in gefitinib-resistant cells (PC9/R, H1299 and A549), but this change in sensitivity was not observed in H1975. Up-regulated HOTAIR induced cell apoptosis in PC9/R, H1299 and A549, and activated epithelial-mesenchymal transition (EMT). CONCLUSIONS: HOTAIR expression was associated with primary and acquired resistance to EGFR-TKIs and could regulate cell proliferation through activating cell apoptosis and EMT, which suggest that HOTAIR might be able to act as a biomarker to predict the EGFR-TKIs resistance.
OBJECTIVE: 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. METHODS: 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. RESULTS: 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 < 0.01] compared with low HOTAIR expression subgroup in tumors which respond to EGFR-TKIs. In vitro, over-expression HOTAIR could restore gefitinib sensitivity in gefitinib-resistant cells (PC9/R, H1299 and A549), but this change in sensitivity was not observed in H1975. Up-regulated HOTAIR induced cell apoptosis in PC9/R, H1299 and A549, and activated epithelial-mesenchymal transition (EMT). CONCLUSIONS: HOTAIR expression was associated with primary and acquired resistance to EGFR-TKIs and could regulate cell proliferation through activating cell apoptosis and EMT, which suggest that HOTAIR might be able to act as a biomarker to predict the EGFR-TKIs resistance.