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Penn Scientists Lead Study Characterizing lncRNAs in Human Cancers

NEW YORK (GenomeWeb) – Changes in long non-coding RNA expression levels are highly indicative of specific cancer types, perhaps even more so than protein-coding genes, according to a new study published today in Cancer Cell.

Scientists led by first authors Xiaohui Yan, Zhongyi Hu, and Yi Feng and senior authors Chi Dan and Lin Zhang, all from the University of Pennsylvania's Perelman School of Medicine, characterized alterations in long non-coding RNAs (lncRNAs) in 5,037 tumor specimens comprising 13 cancer types from The Cancer Genome Atlas. They looked at differential changes to lncRNAs at the transcriptional, genomic, and epigenomic level to identify cancer-driving lncRNAs and predict their function.

The study found 2,316 lncRNAs altered in all 13 cancer types. As part of a more detailed analysis, the study looked at disregulation of lncRNA expression in seven cancers. Expression could be both up-regulated and down-regulated compared to normal cells, with, on average, 15 percent being up-regulated and 11 percent being down-regulated in the cancers.

"These alterations are strikingly cancer-type specific," Zhang said in a statement. The study found that 60 percent of the differentially expressed lncRNAs were specific to a particular cancer type; only five lncRNAs were differentially expressed in all seven types.

The authors wrote that their work could provide a framework for investigating the role of lncRNAs in cancer and lead to new diagnostics.

They noted that prior to the discovery of lncRNAs, research on the drivers of cancer was focused on protein-coding genes. However, they found many mutations outside of those genetic loci. "With non-coding RNA sequences constituting almost three quarters of the human genome, there is a great need to characterize genomic, epigenetic, and other alterations of long non-coding segments," Zhang said. "The present study fills this significant gap in cancer research."

In normal cells, lncRNAs are often expressed only in specific cells. The recent study suggests the same is true for cancer cells. The authors said that expression of lncRNAs was even more specific to cancer type than expression of pseudo- and protein-coding genes. The study also showed that cancers exhibit different DNA methylation patterns in the promoter regions of lncRNA genes and cancer-associated SNPs can be located in lncRNA genomic loci.

This specificity, along with the ease of detecting and quantifying lncRNAs, could lead to precise diagnostics, the authors said. "[Long non-coding RNAs] often form secondary structures that are relatively stable, thereby facilitating their detection as free RNAs in body fluids such as urine and blood. Therefore, lncRNAs may be an ideal class of biomarkers with potential applications in cancer prediction, early detection, diagnosis, and classification," the authors wrote.