FIGNL1 is overexpressed in small cell lung cancer patients and enhances NCI-H446 cell resistance to cisplatin and etoposide

Abnormal DNA repair plays an important role in tumor occurrence, progression and resistance to therapy. Fidgetin-like 1 (FIGNLI) expression was assayed in 42 small cell lung cancer (SCLC) and 45 normal lung specimens from Chinese patients by qRT-PCR. Notably, FIGNLI 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 FIGNLI was adopted to explore the biological significance of FIGNL1 in SCLC. Even when FIGNLI 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 El and CDK2, key cell cycle regulators, were significantly reduced. After downregulation of FIGNLI 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 FIGNLI function of DNA double strand repair. The sensitivity of H446 cells to etoposide and cisplatin was negatively correlated with FIGNLI expression. Meanwhile, an obvious positive correlation between DNA damage severity and the sensitization effect of FIGNLI knockdown was observed. Since FIGNLI is essential in the homologous recombination (HR) pathway, these findings suggest that abnormal activation of the HR pathway featured by FIGNLI overexpression contributes to rapid progression and relapse of SCLC in addition to chemotherapy resistance. Further research assessing the functions and mechanisms of FIGNLI, and other HR pathway genes may disclose unique pathological characteristics of SCLC, and help identify potential therapeutic targets and biomarkers.