Paired box 2 promotes progression of endometrial cancer via regulating cell cycle pathway

J Cancer. 2018 Sep 25;9(20):3743-3754. doi: 10.7150/jca.22418. eCollection 2018.

Abstract

Background: Human paired box 2 (PAX2) plays a key role in cell fate, early patterning and organogenesis. Methods: We investigated the function of PAX2 on the biological behavior of endometrial cancer in vitro and in vivo and to explore the regulation mechanism, stable knocking-down and over-expression PAX2 endometrial cancer cell lines were established. CCK-8 and transwell assays were applied to determine proliferation, invasion and migration ability. Cell cycle distribution was analyzed by flow cytometry. Affymetrix GeneChip® human Exon 1.0 ST arrays was used to screen the downstream target genes of PAX2. Results: PAX2 significantly enhanced proliferation and invasiveness. In addition, PAX2 influenced the expression of cyclin-dependent kinase 1(CDK1), which play pivotal roles in cell cycle pathway. When CDK1 was knocked down, and the cell proliferation promotion role of PAX2 was attenuated dramatically to a level comparable with the control groups. Conclusions: PAX2, though influencing the expression of CDK1, promotes the proliferation, enhances the mobility of endometrial cancer cells, thus exerts an important role in the carcinogenesis of endometrial cancer. PAX2 may be a potential therapeutic target for endometrial cancer.

Keywords: Cell proliferation; Ovarian cancer; PAX2.