American Journal of Pathology
American Journal of Pathology
3 years ago

Overexpression of Flap Endonuclease 1 Correlates with Enhanced Proliferation and Poor Prognosis of Non–Small-Cell Lung Cancer

Flap endonuclease 1 (FEN1) plays a crucial role in both DNA replication and damage repair. In this study, we investigated FEN1 expression and its clinical-pathological significance in non–small-cell lung cancer (NSCLC). Quantitative reverse PCR and immunohistochemistry analysis identified that both FEN1 mRNA and protein were highly over-expressed in about 36% of 136 cancer tissues compared to adjacent tissues in which FEN1 was generally undetectable. Notably, patients with FEN1-overexpressed cancers were prone to have poor differentiation and poor prognosis. A strong positive correlation between the levels of FEN1 and Ki-67 staining was identified in these NSCLC tissues (R = 0.485), suggesting overexpressed FEN1 conferred a proliferative advantage to NSCLC. Furthermore, knockdown of FEN1 resulted in G1/S or G2/M phase cell cycle arrest; suppressed in vitro cellular proliferation in NSCLC cancer cells. Consistently, a selective FEN1 inhibitor was shown to effectively inhibit cellular proliferation of NSCLC cells in a dose-dependent manner. Additionally, knockdown of FEN1 significantly attenuated homologous DNA repair efficiency and enhanced cytotoxic effects of cisplatin in NSCLC cells. Take together; our findings have indicated that overexpressed FEN1 represents a prognostic biomarker and potential therapeutic target for NSCLC treatment, which warrants further study.

Publisher URL: www.sciencedirect.com/science

DOI: S0002944017307022

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