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The cell cycle system is controlled in a timely manner by three groups of cyclins, cyclin dependent kinases and cyclin dependent kinase inhibitors. Abnormal alterations of cell cycle regulatory mechanisms are a common feature of many diseases including numerous tumor types such as ovarian cancer. Although a variety of cell cycle regulatory genes are well known in mammalian species including human and mice, they are not well studied in avian species, especially in laying hens which are recognized as an excellent animal model for research relevant to human ovarian carcinogenesis. Therefore, in the present study, we focused on comparative expression and regulation of expression of candidate genes which might be involved in the cell cycle program in surface epithelial ovarian cancer in laying hens. Our current results indicate that expression levels of cell cycle gene transcripts are greater in cancerous as compared to normal ovaries. In particular, cyclin A2 ( CCNA2 ),  CCND1 ,  CCND2 ,  CCND3 ,  CCNE2 , cyclin dependent kinase 1 ( CDK1 ),  CDK3 ,  CDK5 , cyclin dependent kinases inhibitor 1A ( CDKN1A ) and  CDKN1B  were upregulated predominantly in the glandular epithelia of cancerous ovaries from laying hens. Further, several microRNAs (miRs), specifically  miR-1798 ,  miR-1699 ,  miR-223  and  miR-1744  were discovered to influence expression of  CCND1 ,  CCNE2 ,  CDK1 , and  CDK3  mRNAs, respectively, via their 3′-UTR which suggests that post-transcriptional regulation of gene expression influences their expression in laying hens. Moreover,  miR-1626  influenced CDKN1A expression and  miR-222, miR-1787  and  miR-1812  regulated CDKN1B expression via their 3′-UTR regions. Collectively, results of the present study demonstrate increased expression of cell cycle-related genes in cancerous ovaries of laying hens and indicate that expression of these genes is post-transcriptionally regulated by specific microRNAs.

Distinct Expression Pattern and Post-Transcriptional Regulation of Cell Cycle Genes in the Glandular Epithelia of Avian Ovarian Carcinomas