The human genome contains about 20,000 protein-coding genes – less than 2 percent of the total – but 70 percent of the genome is made into non-coding RNA. Nevertheless, a systematic characterization of these segments, called long non-coding RNAs (lncRNAs), and their alterations in human cancer, is still lacking. Most studies of genomic alterations in cancer have focused on the miniscule portion of the human genome that encodes protein.
The team analyzed lncRNAs at transcriptional, genomic, and epigenetic levels in over 5,000 tumor specimens across the different cancer types and in 935 cancer cell lines. They found that lncRNA alterations are highly tumor- and cell line-specific compared to protein-coding genes. In addition, lncRNA alterations are often associated with changes in epigenetic modifiers that act directly on gene expression.
The team also developed two bioinformatics-based platforms to identify cancer-associated lncRNAs and explore their biological functions. One is a searchable database that incorporates clinical information with lncRNA molecular alterations to generate “short lists” of candidate lncRNAs to study.
The second approach they developed – predicting the biological function of lncRNAs --successfully identified a novel oncogenic lncRNA called BCAL8. They found that BCAL8, when overexpressed, works to promote the cell cycle, which controls cell division.
This part of the study provided not only a proof of concept for their lncRNA search strategy, but also a customizable database for other investigators to look for lncRNAs of interest and investigate their function. This database is called the Cancer LncRNome Atlasand is administered by the Abramson Cancer Center at Penn.
http://www.uphs.upenn.edu/news/News_Releases/2015/10/zhang2/
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