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Article Open Access

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

  • Authors:
    • Jian Ma
    • Jianlei Li
    • Xiaoling Yao
    • Shuangjun Lin
    • Ye Gu
    • Jianfang Xu
    • Zixin Deng
    • Wei Ma
    • Haiping Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200092, P.R. China, State Key Laboratory of Microbial Metabolism, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China, Department of Endoscopy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200092, P.R. China
    Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1935-1942
    |
    Published online on: March 1, 2017
       https://doi.org/10.3892/or.2017.5483
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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.
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1 

Chapman CJ, Thorpe AJ, Murray A, Parsy-Kowalska CB, Allen J, Stafford KM, Chauhan AS, Kite TA, Maddison P and Robertson JF: Immunobiomarkers in small cell lung cancer: Potential early cancer signals. Clin Cancer Res. 17:1474–1480. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Mamdani H, Induru R and Jalal SI: Novel therapies in small cell lung cancer. Transl Lung Cancer Res. 4:533–544. 2015.PubMed/NCBI

3 

Halazonetis TD, Gorgoulis VG and Bartek J: An oncogene-induced DNA damage model for cancer development. Science. 319:1352–1355. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Schvartzman JM, Sotillo R and Benezra R: Mitotic chromosomal instability and cancer: Mouse modelling of the human disease. Nat Rev Cancer. 10:102–115. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Goode EL, Ulrich CM and Potter JD: Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev. 11:1513–1530. 2002.PubMed/NCBI

6 

Yaglom JA, McFarland C, Mirny L and Sherman MY: Oncogene-triggered suppression of DNA repair leads to DNA instability in cancer. Oncotarget. 5:8367–8378. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Scott SP and Pandita TK: The cellular control of DNA double-strand breaks. J Cell Biochem. 99:1463–1475. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Jeggo PA and Löbrich M: How cancer cells hijack DNA double-strand break repair pathways to gain genomic instability. Biochem J. 471:1–11. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Helleday T, Petermann E, Lundin C, Hodgson B and Sharma RA: DNA repair pathways as targets for cancer therapy. Nat Rev Cancer. 8:193–204. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Pleasance ED, Stephens PJ, O'Meara S, McBride DJ, Meynert A, Jones D, Lin ML, Beare D, Lau KW, Greenman C, et al: A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature. 463:184–190. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Byers LA, Wang J, Nilsson MB, Fujimoto J, Saintigny P, Yordy J, Giri U, Peyton M, Fan YH, Diao L, et al: Proteomic profiling identifies dysregulated pathways in small cell lung cancer and novel therapeutic targets including PARP1. Cancer Discov. 2:798–811. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Damia G and D'Incalci M: Targeting DNA repair as a promising approach in cancer therapy. Eur J Cancer. 43:1791–1801. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Hine CM, Seluanov A and Gorbunova V: Use of the Rad51 promoter for targeted anti-cancer therapy. Proc Natl Acad Sci USA. 105:20810–20815. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Richardson C, Stark JM, Ommundsen M and Jasin M: Rad51 overexpression promotes alternative double-strand break repair pathways and genome instability. Oncogene. 23:546–553. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Cox GA, Mahaffey CL, Nystuen A, Letts VA and Frankel WN: The mouse fidgetin gene defines a new role for AAA family proteins in mammalian development. Nat Genet. 26:198–202. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Luke-Glaser S, Pintard L, Tyers M and Peter M: The AAA-ATPase FIGL-1 controls mitotic progression, and its levels are regulated by the CUL-3MEL-26 E3 ligase in the C. elegans germ line. J Cell Sci. 120:3179–3187. 2007. View Article : Google Scholar : PubMed/NCBI

17 

L'Hôte D, Vatin M, Auer J, Castille J, Passet B, Montagutelli X, Serres C and Vaiman D: Fidgetin-like1 is a strong candidate for a dynamic impairment of male meiosis leading to reduced testis weight in mice. PLoS One. 6:e275822011. View Article : Google Scholar : PubMed/NCBI

18 

Yuan J and Chen J: FIGNL1-containing protein complex is required for efficient homologous recombination repair. Proc Natl Acad Sci USA. 110:10640–10645. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Hartwell LH and Kastan MB: Cell cycle control and cancer. Science. 266:1821–1828. 1994. View Article : Google Scholar : PubMed/NCBI

20 

Rajagopalan H and Lengauer C: Aneuploidy and cancer. Nature. 432:338–341. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Lupas AN and Martin J: AAA proteins. Curr Opin Struct Biol. 12:746–753. 2002. View Article : Google Scholar : PubMed/NCBI

22 

Hanson PI and Whiteheart SW: AAA+ proteins: Have engine, will work. Nat Rev Mol Cell Biol. 6:519–529. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Tucker PA and Sallai L: The AAA+ superfamily - a myriad of motions. Curr Opin Struct Biol. 17:641–652. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Snider J and Houry WA: AAA+ proteins: Diversity in function, similarity in structure. Biochem Soc Trans. 36:72–77. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Wendler P, Ciniawsky S, Kock M and Kube S: Structure and function of the AAA+ nucleotide binding pocket. Biochim Biophys Acta. 1823:2–14. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Yachida S, Jones S, Bozic I, Antal T, Leary R, Fu B, Kamiyama M, Hruban RH, Eshleman JR, Nowak MA, et al: Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 467:1114–1117. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Heaphy CM, Bisoffi M, Joste NE, Baumgartner KB, Baumgartner RN and Griffith JK: Genomic instability demonstrates similarity between DCIS and invasive carcinomas. Breast Cancer Res Treat. 117:17–24. 2009. View Article : Google Scholar : PubMed/NCBI

28 

O'Grady S, Finn SP, Cuffe S, Richard DJ, O'Byrne KJ and Barr MP: The role of DNA repair pathways in cisplatin resistant lung cancer. Cancer Treat Rev. 40:1161–1170. 2014. View Article : Google Scholar : PubMed/NCBI

29 

Willers H, Azzoli CG, Santivasi WL and Xia F: Basic mechanisms of therapeutic resistance to radiation and chemotherapy in lung cancer. Cancer J. 19:200–207. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Peters GJ, Avan A, Ruiz MG, Orsini V, Avan A, Giovannetti E and Smit EF: Predictive role of repair enzymes in the efficacy of Cisplatin combinations in pancreatic and lung cancer. Anticancer Res. 34:435–442. 2014.PubMed/NCBI

31 

Eastman A: The formation, isolation and characterization of DNA adducts produced by anticancer platinum complexes. Pharmacol Ther. 34:155–166. 1987. View Article : Google Scholar : PubMed/NCBI

32 

Hurwitz JL, McCoy F, Scullin P and Fennell DA: New advances in the second-line treatment of small cell lung cancer. Oncologist. 14:986–994. 2009. View Article : Google Scholar : PubMed/NCBI

33 

Martin SA, Lord CJ and Ashworth A: DNA repair deficiency as a therapeutic target in cancer. Curr Opin Genet Dev. 18:80–86. 2008. View Article : Google Scholar : PubMed/NCBI

34 

Madhusudan S and Middleton MR: The emerging role of DNA repair proteins as predictive, prognostic and therapeutic targets in cancer. Cancer Treat Rev. 31:603–617. 2005. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ma J, Li J, Yao X, Lin S, Gu Y, Xu J, Deng Z, Ma W and Zhang H: FIGNL1 is overexpressed in small cell lung cancer patients and enhances NCI-H446 cell resistance to cisplatin and etoposide. Oncol Rep 37: 1935-1942, 2017.
APA
Ma, J., Li, J., Yao, X., Lin, S., Gu, Y., Xu, J. ... Zhang, H. (2017). FIGNL1 is overexpressed in small cell lung cancer patients and enhances NCI-H446 cell resistance to cisplatin and etoposide. Oncology Reports, 37, 1935-1942. https://doi.org/10.3892/or.2017.5483
MLA
Ma, J., Li, J., Yao, X., Lin, S., Gu, Y., Xu, J., Deng, Z., Ma, W., Zhang, H."FIGNL1 is overexpressed in small cell lung cancer patients and enhances NCI-H446 cell resistance to cisplatin and etoposide". Oncology Reports 37.4 (2017): 1935-1942.
Chicago
Ma, J., Li, J., Yao, X., Lin, S., Gu, Y., Xu, J., Deng, Z., Ma, W., Zhang, H."FIGNL1 is overexpressed in small cell lung cancer patients and enhances NCI-H446 cell resistance to cisplatin and etoposide". Oncology Reports 37, no. 4 (2017): 1935-1942. https://doi.org/10.3892/or.2017.5483
Copy and paste a formatted citation
x
Spandidos Publications style
Ma J, Li J, Yao X, Lin S, Gu Y, Xu J, Deng Z, Ma W and Zhang H: FIGNL1 is overexpressed in small cell lung cancer patients and enhances NCI-H446 cell resistance to cisplatin and etoposide. Oncol Rep 37: 1935-1942, 2017.
APA
Ma, J., Li, J., Yao, X., Lin, S., Gu, Y., Xu, J. ... Zhang, H. (2017). FIGNL1 is overexpressed in small cell lung cancer patients and enhances NCI-H446 cell resistance to cisplatin and etoposide. Oncology Reports, 37, 1935-1942. https://doi.org/10.3892/or.2017.5483
MLA
Ma, J., Li, J., Yao, X., Lin, S., Gu, Y., Xu, J., Deng, Z., Ma, W., Zhang, H."FIGNL1 is overexpressed in small cell lung cancer patients and enhances NCI-H446 cell resistance to cisplatin and etoposide". Oncology Reports 37.4 (2017): 1935-1942.
Chicago
Ma, J., Li, J., Yao, X., Lin, S., Gu, Y., Xu, J., Deng, Z., Ma, W., Zhang, H."FIGNL1 is overexpressed in small cell lung cancer patients and enhances NCI-H446 cell resistance to cisplatin and etoposide". Oncology Reports 37, no. 4 (2017): 1935-1942. https://doi.org/10.3892/or.2017.5483
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