| To date, cancer research has focused on alterations of protein coding genes. However, recent evidence suggests that alterations of non-coding RNA, particularly micro-RNAs (miRNAs), also contribute to tumorigenesis. For example, an oncogenic polycistronic miRNA cluster, mir-17-92, cooperates with c-myc to accelerate B-cell lymphomas in mice. There's also evidence that miRNAs such as mir-15, mi-16, and let-7 function as tumor suppressors. Together with Dr. Lin He, I have identified the mir-34 family as direct transcriptional target genes of the tumor suppressor p53 for mediating cell-cycle arrest. Using retroviral expression vectors, I showed that constitutive or conditional expression of miR-34a in murine liver tumor cells resulted in delayed tumor progression, suggesting delivery of miR-34a as a potential therapeutic tool. To study the loss-of function phenotype of miR-34a, I generated knockout animals harboring genetic ablation of miR-34a. I also performed a genome wide miRNA screen and identified candidate oncogenic miRNAs. My thesis work established miR-34a as an essential component of the p53 tumor suppressor network and emphasized the importance of miRNAs in human cancer. |
