ICIBM 2016

Wei Li, Ph.D.

Baylor College of Medicine
Friday, December 9, 2016
9:40 am - 10:00 am


Dr. Li is a professor at Baylor College of Medicine. His research is focused on the design and application of bioinformatics algorithms to elucidate global regulatory mechanisms in development and diseases such as cancer. He has a solid track record in large-scale genomics and epigenomics data analysis, and in developing widely used open-source bioinformatics software. In collaboration with experimental biologists, he has used big data bioinformatics analysis to gain novel biological insights in development, aging, stem cell, neurologic disorders, as well as breast, prostate, brain and blood cancers. Since establishing my own bioinformatics lab in early 2008, he has published more than 60 peer-reviewed papers through solid methodology development and extensive collaboration research, including 22 in Nature, Science and Cell series.

3'-UTR Shortening Represses Tumor Suppressors in trans by Disrupting ceRNA Crosstalk

Widespread mRNA 3'-UTR shortening through alternative polyadenylation (APA) promotes tumor growth in vivo. A prevailing hypothesis is that it induces proto-oncogene in cis through escaping microRNA-mediated repression but this view has been challenged by recent APA data. Here we show that shortened 3'-UTRs in breast cancers are strongly associated with repression of tumor suppressors enriched in competing endogenous RNAs (ceRNAs). Our model-based analysis of the trans effect of 3'-UTR shortening (MAT3UTR) reveals its dominant role in altering ceRNA expression. MAT3UTR predicts many trans-targets of 3'-UTR shortening, including PTEN, a crucial tumor suppressor involved in ceRNA crosstalk. Importantly, knockdown of NUDT21 (also known as CFIm25), a master 3'-UTR shortening regulator, can direct the release of microRNAs to repress the tumor suppressor PHF6 in trans in a miRNA dependent manner. Together, our big data analysis followed by functional validation suggests that the major role of 3'-UTR shortening in tumorigenesis is to repress tumor suppressors in trans, rather than induce proto-oncogenes in cis.