Functions and epigenetic aspects of miR-15/16: Possible future cancer therapeutics

MicroRNA 15 and 16 controls cell-cycle by binding to Cyclin D1, cyclin E, BCL2, c-Myc, E2F. Further deletion of miR-15/16 accelerates cell growth through modulation of cell-cycle proteins such as Cyclin E, Cyclin D1, D3 and cdk6 involving E2F. The expression of miR-15/16 inhibits cell proliferation, suppresses tumorigenicity and induces apoptosis in CLL cancer cells, prostate cancer cells, and pituitary adenomas by targeting genes including BCL2, CCND1, MCl-1 and WNT 3a. Studies have found that restoration of mir-15/miR-16 by microRNA mimics inhibits Bcl-2 proteins and enhances the expression of Caspase proteins indicating the apoptotic inducing nature of miR-15/16. Overexpression of cell-cycle kinases WEE1 and CHK1 occurs commonly in Cisplatin-resistant cells miR-15/16/195/424/497 family are found to sensitizes Cisplatin-resistant cells to apoptosis by targeting WEE and CHK1. MiR-15/16 controls tumor angiogenesis and cause colon cancer xenograft growth arrest. MiR-15/16 is involved in several signaling cascade pertaining to cancer such as NF-kβ, TNF, SOCS and Wnt.150