MicroRNAs: Small Molecules with Big Impacts in Cancer Development
Authors:Alex So, Catherine Bingchan Xie
Mentor:David Baltimore, Robert Andrews Millikan Professor of Biology; President Emeritus, California Institute of Technology
The mammalian inflammatory response is a complex and rapid physiological reaction to noxius stimuli. MicroRNAs are emerging as key regulators of the immune system. MicroRNAs are a large class of 21-25 nucleotide small ribonucleic acids that post-transcriptionally regulate a diverse array of genes. As microRNAs control the regulation of fundamental processes, their dysregulation has now clearly been linked to cancer and particularly to leukemia. Our broad objective is to identify and characterize miRNAs that promote leukemic development. We are cloning a genome wide library of more than 700 miRNAs into the murine stem-cell virus-GFP expression vector. This vector design allows for the expression of the miRNAs and GFP off the same transcript, allowing the tracking of miRNA over-expression within cells as a function of GFP positivity. To screen for miRNAs that induce tumorigenesis, we first use an in vitro system and over-express the miRNAs individuals in primary mouse bone marrow cells. We then isolate those that accelerate cell proliferation, a hallmark of tumorigenesis for further validation. The putative miRNAs identified in the initial screen are then subjected to further studies to determine whether they induce leukemia in mice. Our study will provide an in-depth network of miRNAs that regulate leukemogenesis and have crucial implications in cancer therapy.