title: Genome-wide transcript profiling reveals novel breast cancer-associated intronic sense RNAs.
abstract: 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.
authors: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, United States of America.
authors: Sang Woo
authors: SW
authors: Kim
authors: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, United States of America.
authors: Elane
authors: E
authors: Fishilevich
authors: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, United States of America.
authors: Gustavo
authors: G
authors: Arango-Argoty
authors: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, United States of America.
authors: Yuefeng
authors: Y
authors: Lin
authors: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, United States of America.
authors: Guodong
authors: G
authors: Liu
authors: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, United States of America.
authors: Zhihua
authors: Z
authors: Li
authors: Department of Neurobiology, University of Pittsburgh, 3501 Fifth Ave, Pittsburgh, Pennsylvania 15260, United States of America.
authors: A Paula
authors: AP
authors: Monaghan
authors: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, United States of America.
authors: Mark
authors: M
authors: Nichols
authors: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, United States of America.
authors: Bino
authors: B
authors: John
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D052004:Bone Morphogenetic Protein Receptors; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007438:Introns; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D000074165:Zinc Finger E-box Binding Homeobox 2; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D052004:Bone Morphogenetic Protein Receptors; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D000074165:Zinc Finger E-box Binding Homeobox 2; D000099162:Endothelial PAS Domain-Containing Protein 1; C486175:CRIM1 protein, human; C086384:RBMS1 protein, human; C101059:RFX2 protein, human; C492363:ZEB2 protein, human