Dysregulation of Krüppel-like factor 12 in the development of endometrial cancer

Abstract

Objective: Endometrial cancer (EC) remains a malignancy with poor survival outcome. To investigate the role of Krüppel-like factor 12 (KLF12), a transcription factor, in the progression of human EC.

Methods: Immunohistochemistry, real time-PCR and western blot analysis of KLF12 expression in EC patients' tissues. Bioinformatics analysis revealed the clinical importance of KLF12 expression and survival ratio. Overexpression of KLF12 was generated using the ViraPower Adenoviral Expression System in EC cell lines. Cell viability assay, cell apoptosis assay and cell migration assay were used to determine cell proliferation, cell apoptosis and cell migration, respectively. Western blot analysis was carried out to determine the protein levels in cell lines and animal tissues.

Results: The expression of KLF12 was observed to be much higher in human EC tissues compared with normal endometrium. Moreover, KLF12 expression was correlated positively with disease recurrence and was also associated with decreased survival probability. The overexpression of KLF12 in EC cell lines resulted in increased cell proliferation, decreased cell apoptosis and enhanced cell migration. Furthermore, overexpression of KLF12 also increased tumor size in vivo. Moreover, up-regulation of KLF12 dramatically increased the expression levels of MMP2, MMP9, pAKT S473 and CCND1. Our research reveals that overexpressed KLF12 contributes the growth of EC tumor by activating AKT signaling and increasing CCND1expression level.

Conclusions: To our knowledge, this is the first study to explore the significance of KLF12 in the development of EC, and KLF12 is expected to provide a novel potential therapeutic target for EC treatment.

Keywords: AKT signaling; Endometrial cancer; KLFs.