जर्नल ऑफ बायोकैमिस्ट्री एंड सेल बायोलॉजी

अमूर्त

Cyclin A1 Expression is Reciprocally Controlled by the Transcription Factor ZNF217 and miRNAs in Invasive Breast and Prostate Cancer Cells: An In Silico Analysis

Tsolkas G, Komninou D, Papanikolaou NA

Cyclins and their partner cyclin-dependent kinases (CDKs) play crucial roles in proliferation, initiation of DΝΑ replication, and mitosis. Human cyclin Α1 is expressed at its highest levels in spermatocytes and is re-expressed in leukemic cell lines, in cells from acute myeloid leukemia (ΑΜL) and acute promyelocytic leukemia (ΑΡL), as well as in metastatic breast cancer, hepatocarcinomas and prostate cancer. Transgenic mice engineered to express cyclin Α1 in myeloid precursor cells develop ΑΜL with low penetrance and long latency. In this work we have mined and analyzed data from the Gene Expression Omnibus (GEO) that potentially reveal novel cyclin A1 mechanisms of action in metastatic breast and prostate tumors. The data suggest that in breast and prostate tumors, cyclin A1 expression is repressed by two miRNAs and activated by the transcription factor ZNF217, and that cyclin A1 is overexpressed in invasive prostate cancer but not in pre-invasive carcinoma. Down-regulation of the miRNAs and overexpression of ZNF217 correlate with epithelial-to-mesenchymal transition (EMT), suggesting that EMT may be partly mediated by ZNF217-mediated re-expression of cyclin A1. Collectively, these data argue that re-expression of cyclin A1 protein may contribute to the mesenchymal-to-epithelial transition in the aforementioned tumor types. Since cyclin A1 protein is not expressed in normal adult tissues, except germ cells, it may be a promising target for intervention. We discuss implications of these findings in further dissecting the role of cyclin A1 protein in cancer development and for its targeting.