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Genome-wide transcript profiling reveals novel breast cancer-associated intronic sense RNAs

Kim, SW and Fishilevich, E and Arango-Argoty, G and Lin, Y and Liu, G and Li, Z and Monaghan, AP and Nichols, M and John, B (2015) Genome-wide transcript profiling reveals novel breast cancer-associated intronic sense RNAs. PLoS ONE, 10 (3).

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Non-coding RNAs (ncRNAs) play major roles in development and cancer progression. To identify novel ncRNAs that may identify key pathways in breast cancer development, we performed high-throughput transcript profiling of tumor and normal matched-pair tissue samples. Initial transcriptome profiling using high-density genome-wide tiling arrays revealed changes in over 200 novel candidate genomic regions that map to intronic regions. Sixteen genomic loci were identified that map to the long introns of five key protein-coding genes, CRIM1, EPAS1, ZEB2, RBMS1, and RFX2. Consistent with the known role of the tumor suppressor ZEB2 in the cancer-associated epithelial to mesenchymal transition (EMT), in situ hybridization reveals that the intronic regions deriving from ZEB2 as well as those from RFX2 and EPAS1 are down-regulated in cells of epithelial morphology, suggesting that these regions may be important for maintaining normal epithelial cell morphology. Paired-end deep sequencing analysis reveals a large number of distinct genomic clusters with no coding potential within the introns of these genes. These novel transcripts are only transcribed from the coding strand. A comprehensive search for breast cancer associated genes reveals enrichment for transcribed intronic regions from these loci, pointing to an underappreciated role of introns or mechanisms relating to their biology in EMT and breast cancer.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Kim, SW
Fishilevich, Efishily@pitt.eduFISHILY
Arango-Argoty, G
Lin, Y
Liu, G
Li, Z
Monaghan, AP
Nichols, Mmnichols@pitt.eduMNICHOLS
John, B
ContributionContributors NameEmailPitt UsernameORCID
Date: 23 March 2015
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS ONE
Volume: 10
Number: 3
DOI or Unique Handle: 10.1371/journal.pone.0120296
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Medicine
School of Medicine > Neurobiology
School of Medicine > Pharmacology and Chemical Biology
Refereed: Yes
Date Deposited: 23 Aug 2016 13:54
Last Modified: 30 Mar 2021 14:56


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