Dicer in Mammary Tumor Stem Cell Maintenance

摘要

To date, most cancer research has focused on alterations in the sequence, gene structure, copy number and expression of protein coding genes. However, we find increasingly that the genome generates a diversity of non- coding RNAs, many of which have unknown functions. MicroRNAs (miRNAs), which are small, 21-24nt RNAs generated by the key enzyme Dicer, represent a prominent class of such non-coding RNAs. There's evidence suggesting that miRNAs could collaborate with oncogenes to facilitate tumor formation. On the other hand, several miRNAs are found to function as tumor suppressors. Our previous study revealed a miRNA family, miR-34, as direct transcriptional target of p53, the master tumor suppressor gene. To address the role of miR-34 in cancer formation and maintenance, we generated cell lines over express miR- 34. We have demonstrated that ectopic expression of miR-34 in both primary and tumor cell lines can induce growth arrest through repression of cell cycle genes, and we have shown in animal model that tumor cells over expressing miR- 34 have disadvantage in tumor initiation and maintenance. Our work placed miRNAs as one of the central mediators of p53 tumor suppressor network, which plays an important role in many cancer types, including breast cancer.