title: Globally increased ultraconserved noncoding RNA expression in pancreatic adenocarcinoma.
abstract: Transcribed ultraconserved regions (T-UCRs) are a class of non-coding RNAs with 100% sequence conservation among human, rat and mouse genomes. T-UCRs are differentially expressed in several cancers, however their expression in pancreatic adenocarcinoma (PDAC) has not been studied. We used a qPCR array to profile all 481 T-UCRs in pancreatic cancer specimens, pancreatic cancer cell lines, during experimental pancreatic desmoplasia and in the pancreases of P48Cre/wt; KrasLSL-G12D/wt mice. Fourteen, 57 and 29% of the detectable T-UCRs were differentially expressed in the cell lines, human tumors and transgenic mouse pancreases, respectively. The vast majority of the differentially expressed T-UCRs had increased expression in the cancer. T-UCRs were monitored using an in vitro model of the desmoplastic reaction. Twenty-five % of the expressed T-UCRs were increased in the HPDE cells cultured on PANC-1 cellular matrix. UC.190, UC.233 and UC.270 were increased in all three human data sets. siRNA knockdown of each of these three T-UCRs reduced the proliferation of MIA PaCa-2 cells up to 60%. The expression pattern among many T-UCRs in the human and mouse pancreases closely correlated with one another, suggesting that groups of T-UCRs are co-activated in PDAC. Successful knockout of the transcription factor EGR1 in PANC-1 cells caused a reduction in the expression of a subset of T-UCRs suggesting that EGR1 may control T-UCR expression in PDAC. We report a global increase in expression of T-UCRs in both human and mouse PDAC. Commonalties in their expression pattern suggest a similar mechanism of transcriptional upregulation for T-UCRs in PDAC.
authors.affiliation: College of Pharmacy, University of Florida, Gainesville, FL, USA.
authors.forename: Jinmai
authors.initials: J
authors.lastname: Jiang
authors.affiliation: College of Pharmacy, Ohio State University, Columbus, OH, USA.|Present address: Department of Molecular Biology University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Ana Clara P
authors.initials: AC
authors.lastname: Azevedo-Pouly
authors.affiliation: University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Roxana S
authors.initials: RS
authors.lastname: Redis
authors.affiliation: College of Pharmacy, Ohio State University, Columbus, OH, USA.|Present address: College of Pharmacy and Wonkwang Oriental Medicines Research Institute, Wonkwang University, Republic of Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Lombardi Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Gusev
authors.affiliation: Cambridge University, Cambridge, UK.
authors.forename: David
authors.initials: D
authors.lastname: Allard
authors.affiliation: College of Pharmacy, Ohio State University, Columbus, OH, USA.
authors.forename: Dhruvitkumar S
authors.initials: DS
authors.lastname: Sutaria
authors.affiliation: College of Pharmacy, Ohio State University, Columbus, OH, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Badawi
authors.affiliation: College of Pharmacy, Ohio State University, Columbus, OH, USA.
authors.forename: Ola A
authors.initials: OA
authors.lastname: Elgamal
authors.affiliation: Veterans Affairs Medical Center, Oklahoma City, OK, USA.|Department of Surgery, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors.forename: Megan R
authors.initials: MR
authors.lastname: Lerner
authors.affiliation: Veterans Affairs Medical Center, Oklahoma City, OK, USA.|Department of Surgery, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Brackett
authors.affiliation: University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.affiliation: College of Pharmacy, University of Florida, Gainesville, FL, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Schmittgen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008822:Mice, Transgenic; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D022661:RNA, Untranslated / Q000235:genetics*; D051381:Rats
chemical_list: D022661:RNA, Untranslated
keywords: EGR1; noncoding RNA; pancreas cancer; ultraconserved elements