Oncogenic activity of MCM7 transforming cluster.

The miniature chromosome maintenance (MCM) complex is a group of proteins that are essential for DNA replication licensing and control of cell cycle progression from G1 to S phase. Recent studies suggest that MCM7 is overexpressed and amplified in a variety of human malignancies. MCM7 genome sequence contains a cluster of miRNA that has been shown to downregulate expression of several tumor suppressors including p21, E2F1, BIM and pTEN. The oncogenic potential of MCM7 and its embedded miRNA has been demonstrated vigorously in in vitro experiments and in animal models, and they appear to cooperate in initiation of cancer. MCM7 protein also serves as a critical target for oncogenic signaling pathways such as androgen receptor signaling, or tumor suppressor pathways such as integrin α7 or retinoblastoma signaling. This review analyzes the transforming activity and signaling of MCM7, oncogenic function of miRNA cluster that is embedded in the MCM7 genome, and the potential of gene therapy that targets MCM7.