Abnormal expression and potential clinical value of oncogenic Krüppel-like factor-5 in lung squamous cell carcinoma

肺鳞状细胞癌中致癌性 Krüppel 样因子-5 的异常表达及其潜在临床价值

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Abstract

BACKGROUND: Krüppel-like factor-5 (KLF5) is a zinc-finger transcription factor related to tumor progression. However, the relationship between KLF5 and lung cancer remains to be identified. AIM: To investigate the clinical value of KLF5 and interference with KLF5 mRNA transcription on the effects of biological behaviors in lung squamous-cell carcinoma (LUSC). METHODS: Lung KLF5 mRNA data were extracted from bioinformatics databases. Blood and tissues from a cohort of patients with benign or malignant lung diseases were collected with ethical committee consent to validate KLF5 expression via multiplex immunofluorescence and immunohistochemistry, Western blot, Enzyme-Linked Immunosorbent Assay or quantitative polymerase chain reaction. Furthermore, KLF5 mRNA was silenced in lung A549 cells to validate biological behaviors in vitro and nude mouse xenograft growth in vivo, respectively. RESULTS: A cohort of bioinformatics databases revealed high KLF5 mRNA expression in LUSC (P < 0.001) but lower KLF5 mRNA expression in lung adenocarcinoma. Upregulated KLF5 in the lung or sera of patients with lung cancer (P < 0.001) were confirmed that related to poor differentiation, lymph node or distant metastasis. Furthermore, the incidence of KLF5 levels greater than 500 ng/mL in LUSC patients was 86.7%, which was significantly greater (P < 0.001) than that in cases with benign lung diseases (13.3%) or healthy controls. Functionally, silencing KLF5 mRNA with a specific shRNA significantly suppressed A549 cell proliferation, decreased cell migration, increased the ratio of G2 phase cells in vitro, and inhibited the growth of nude mouse xenografts in vivo. CONCLUSION: KLF5 is a novel diagnostic biomarker or potential therapeutic target for LUSC.

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