Researchers Seek Disease Biomarkers Hidden in the Long Noncoding RNA Segment of the Genome

Researchers have analyzed the large segment of DNA in the human genome that underlies the species of nucleic acids called long noncoding RNAs (lncRNA), a genre that functions as important regulators of tissue physiology and disease processes including cancer.

To delineate genome-wide lncRNA expression, investigators at the University of Michigan (Ann Arbor, USA) evaluated 7,256 RNA sequencing (RNA-seq) libraries from tumors, normal tissues, and cell lines comprising over 43 terabytes of nucleotide sequence from 25 independent studies.

Evaluation of this data set, as described in the January 19, 2015, online edition of the journal Nature Genetics, yielded a consensus human transcriptome of 91,013 expressed genes. Over 68% (58,648) of genes were classified as coding for lncRNAs, of which 79% were previously unannotated. About 1% (597) of the lncRNAs harbored ultraconserved elements, and 7% (3,900) overlapped disease-associated SNPs (single nucleotide polymorphisms). The complete dataset, named the MiTranscriptome compendium, has been made available to the scientific community online (Please see Related Links below).

To prioritize lineage-specific, disease-associated lncRNA expression, the investigators employed nonparametric differential expression testing and nominated 7,942 lineage- or cancer-associated lncRNA genes. One lncRNA, SChLAP1, was identified as a potential biomarker for aggressive prostate cancer. This RNA was more highly expressed in metastatic prostate cancer than in early stage disease and was found primarily in prostate cancer cells, not in other cancers or normal cells.

"Some long non-coding RNAs tend to be exquisitely specific for cancer, while protein-coding genes are often not. That is what makes lncRNAs a very promising target for developing biomarkers," said senior author Dr. Arul M. Chinnaiyan, professor of pathology at the University of Michigan. "We hope that researchers will investigate the MiTransciptome compendium and begin to nominate lncRNAs for further study and development. It is likely that only a subset of these has true function but as a previously untapped area, it holds great promise. We know about protein-coding genes, but that represents only 1%–2% of the genome. Much less is known about the biology of the noncoding genome in terms of how it might function in a human disease like cancer."

Related Links:
University of Michigan
MiTranscriptome