Upregulation HOXA10 homeobox gene in endometrial cancer: role in cell cycle regulation

Homeobox genes encode a group of transcription factors that regulate embryonic development, organ differentiation and cell proliferation. Some researchers found that homeobox gene family could regulate the expression of cell cycle-related factors which are involved in tumorigenesis. The aim of the present study was to determine whether HOXA10 gene could regulate the expression of p21 and control the cell cycle in endometrial cancer. Real-time PCR and Western blot were used to analyze HOXA10 and p21 gene expression in tissue samples of normal endometrium and endometrial cancer. Upregulate and downregulate HOXA10 gene in endometrial cancer cells by HOXA10-vector and HOXA10-siRNA, p21 mRNA and protein expression were tested by real-time PCR and Western blot. FCM analyze the cell cycle alteration, and cell count and EdU assay were recruited to detect cell proliferative activity after upregulation of HOXA10. Expression of HOXA10 and p21 gene decreased in endometrial cancer, and the expression level of HOXA10 was correlated with cancer grade. The percentage of G1 phase cells increased, and cell proliferative activity decreased after upregulate HOXA10 expression. The expression of p16, p27, Myc, Cyclin D1, Cyclin E, CDK2, CDK4 and CDK6 did not alter after upregulation HOXA10. P21 gene mRNA and protein increased/decreased after upregulation/downregulation HOXA10 expression in cancer cells. HOXA10 regulates G1 phase arrest in endometrial cancer which may be mediated by p21.