microRNA's join the p53 network - another piece in the tumour-suppression puzzle

MiRNA’s are small non-coding regulatory RNA’s that mediate post-transcriptional silencing. They show reduced expression in tumor cells and the components of miRNA biogenesis machinery are suppressed in cancer cells. Recently five independent studies have shown that miR-34 (a miRNA ) is a component of the p53 tumor-suppressor network. The p53 network was thought to consist of only proteins and is activated by many cancer associated stress signals like DNA damage, oncogene activation and hypoxia. MiR-34 was identified as a p53 transcriptional target that can regulate cell proliferation and cell death.

Over expression of miR-34 in fibroblasts and tumor cell lines produced cell arrest followed by apoptosis in some of the cell lines. Microarray analysis showed that miR-34 down-regulated hundreds of mRNAs for cell cycle regulators. Minimal miR-34 deletions have been found in human breast and lung cancer cells and alterations in miR-34 are found in tumor cell lines that have wild-type p53.The discovery that miR-34 was part of the p53 network also cleared up a long standing mystery of the speed at which activated p53 was able to repress a large number of genes.

Comparative analysis of genomes shows that non-coding RNA’s are more represented in complex genomes. Non-coding RNA’s are being recognized as key players in tumor development and since they can affect many targets they can possibly regulate many aspects of a particular cellular process simultaneously.

I chose this paper because it gave me a new understanding of a well known tumor suppressor pathway. Even though miRNAs were first discovered about 15 years ago we still do not completely understand their full function. Scientists have identified over 200 different miRNAs with very specific regulatory functions and I hope that some of these will help us understand how to fix cells when they become cancerous. Lin He, one of the authors of this paper just joined the MCB Department at Berkeley.