Krüppel-Like Factor 5 Promotes Lung Tumorigenesis through Upregulation of Sox4

Abstract

Background: Krüppel-like factor 5 (KLF5), a member of zinc finger class of DNA-binding transcriptional regulators, has attracted attention because of its important regulatory activities linked to diverse functions such as cell growth, proliferation, differentiation, apoptosis and tumorigenesis in a number of systems. However, its biological functions in the initiation and progression of lung tumorigenesis remain largely unexplored. Methods: Quantitative realtime PCR and Western Blot were used to detect the expression of KLF5 in lung cancer tissues and cell lines. Retro-viruses were used to generate KLF5 stable expression lung cancer cell line. Small interfering RNA was used to silence the expression of KLF5 and Sox4. BrdU assay was used to determine the proliferation of cells. Luciferase and Chromatin immunoprecipitation assays were used to detect the regulation of Sox4 by KLF5. Results: KLF5 was up-regulated in lung cancer tissues and cell lines. Overexpression of KLF5 promotes while knockdown of its expression inhibits cell proliferation in two cell lines derived from lung carcinoma. At the molecular level, our results revealed that KLF5 positively regulates Sox4 expression through a transcriptional mechanism. Sox4 deficiency blocked the proliferative roles of KLF5 in lung cancer cells. Conclusion: our data identified the KLF5/Sox4 regulatory signaling play an important role in lung tumorigenesis, which might represent novel therapeutic targets to manage lung carcinoma.