title: Transcriptome analysis of EGFR tyrosine kinase inhibitors resistance associated long noncoding RNA in non-small cell lung cancer.
abstract: The non-small cell lung cancer (NSCLC) patients harbor mutations in the epidermal growth factor receptor (EGFR) can be therapeutically targeted by EGFR tyrosine kinase inhibitors (EGFR-TKI), such as gefitinib, and show improved progression-free survival. However, most of the patients who are initially responsive to EGFR TKIs with activating EGFR mutations eventually develop acquired resistance after long-term therapy, and are followed by disease progression. Recently, diverse mechanisms of acquired EGFR TKI resistance have been reported, but little is known about the role of long noncoding RNAs in EGFR TKIs resistance. To gain insight into the expression pattern and potential function of lncRNAs in NSCLC cells EGFR-TKI resistance, we analyzed expression patterns in EGFR-TKIs-resistant cell lines and compared it with their parental sensitive cell line by using gene profiling datasets from Gene Expression Omnibus (GEO). Then, the expression levels of five chose lncRNAs were validated in PC9-gefitinib resistant cells (PC9G) and sensitive cells by using real-time quantitative PCR (qPCR). Among of these five lncRNAs, CASC9 expression was upregulated in PC9G and knockdown of its expression could increase the sensitivity of PC9G cells to gefitinib, while EWAST1 (LINC00227) is downregulated in PC9G cells and overexpressed EWAST1 also lead to increased sensitivity of PC9G cells to gefitinib. As indicated by GO analysis, the CASC9 and EWAST1 co-expressed genes are involved in several important pathways including regulation of cell growth, regulation of cell apoptosis and Chromatin assembly. Taken together, dysregulated lncRNAs play critical roles in EGFR-TKIs resistant NSCLC cells and might be used as novel potential targets to reverse EGFR-TKI resistance for NSCLC patients.
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Pei
authors.initials: P
authors.lastname: Ma
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Fengqi
authors.initials: F
authors.lastname: Nie
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Zebo
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China. Electronic address: real.lw@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Oncology, Xuzhou Central Hospital, Affiliated Xuzhou Hospital, College of Medicine, Southeast University, Xuzhou, People's Republic of China. Electronic address: hanliang801223@foxmail.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Han
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride / Q000494:pharmacology; D000077156:Gefitinib; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D062085:RNA, Long Noncoding; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: EGFR-TKIs; NSCLC; Resistant; lncRNA