TIGP--Genome wide discovery of miRNAs in animal genomes and functional studies in human cancers
- LecturerDr. Wen-Chang Lin (Institute of Biomedical Sciences, Academia Sinica)
Host: Miss Elsa Pan - Time2010-12-16 (Thu.) 14:00 – 15:00
- LocationAuditorium 106 at new IIS Building
Abstract
Abstract:
MicroRNAs (miRNAs) are endogenous non-protein-coding RNAs of
approximately 22 nucleotides. Thousands of miRNA genes have been
identified (computationally and/or experimentally) in a variety of
organisms, which suggests that miRNA genes have been widely shared
and distributed among species. Our laboratory has applied mature
miRNA sequence patterns to scan the genome sequences of 56 bilaterian
animal species for identification of candidate miRNAs. The regions
centered surrounding these candidate miRNAs were then extracted for
folding and calculating the features of their secondary structure.
Using a support vector machine as a classifier combined with these
features, we identified more than 15,000 orthologous or paralogous
candidate pre-miRNAs, as well as their corresponding candidate mature
miRNAs. Stem-loop RT-PCR and deep sequencing methods were used to
experimentally validate the prediction results in human, medaka and
rabbit. In addition, we have identified 38 methylation-associated
miRNAs in human gastric cancer cells. The methylation-silenced
expression of these microRNAs could be reactivated in gastric cancer
cells by treatment with demethylating drugs in time-dependent manner.
Analysis of the methylation status of these miRNAs showed that the
upstream CpG-rich regions of several miRNAs are frequently methylated
in gastric cancer tissues compared with adjacent normal tissues, and
their methylation status correlated inversely with their expression
patterns. These miRNAs silenced by tumor-specific methylation could
play significant oncogenesis roles in gastric cancer progression.