title: FIGNL1 is overexpressed in small cell lung cancer patients and enhances NCI-H446 cell resistance to cisplatin and etoposide.
abstract: Abnormal DNA repair plays an important role in tumor occurrence, progression and resistance to therapy. Fidgetin-like 1 (FIGNL1) expression was assayed in 42 small cell lung cancer (SCLC) and 45 normal lung specimens from Chinese patients by qRT-PCR. Notably, FIGNL1 was upregulated by 1.5-fold in the SCLC specimens compared to that noted in the normal counterparts. The SCLC cell line NCI-H446 that overexpresses FIGNL1 was adopted to explore the biological significance of FIGNL1 in SCLC. Even when FIGNL1 expression was suppressed by up to 48.6%, H446 cell growth was increased by only 10-16%. Although no significant changes in cell cycle distribution were observed in the H446 cells, the levels of cyclin E1 and CDK2, key cell cycle regulators, were significantly reduced. After downregulation of FIGNL1 expression by 13.5% in the H446 cells, the cells were 61.8% (24 h) to 29.1% (48 h) more sensitive to etoposide and cisplatin, respectively, consistent with the FIGNL1 function of DNA double-strand repair. The sensitivity of H446 cells to etoposide and cisplatin was negatively correlated with FIGNL1 expression. Meanwhile, an obvious positive correlation between DNA damage severity and the sensitization effect of FIGNL1 knockdown was observed. Since FIGNL1 is essential in the homologous recombination (HR) pathway, these findings suggest that abnormal activation of the HR pathway featured by FIGNL1 overexpression contributes to rapid progression and relapse of SCLC in addition to chemotherapy resistance. Further research assessing the functions and mechanisms of FIGNL1, and other HR pathway genes may disclose unique pathological characteristics of SCLC, and help identify potential therapeutic targets and biomarkers.
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Microbial Metabolism, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Jianlei
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Microbial Metabolism, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Microbial Metabolism, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Shuangjun
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Endoscopy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Microbial Metabolism, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Zixin
authors.initials: Z
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Microbial Metabolism, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Haiping
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000096:biosynthesis* / Q000235:genetics; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D059765:Homologous Recombination / Q000235:genetics; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology
chemical_list: D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D005047:Etoposide; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C583279:FIGNL1 protein, human; D002945:Cisplatin