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Expression Profiling Identifies the Noncoding Processed Transcript of HNRNPU with Proliferative Properties in Pancreatic Ductal Adenocarcinoma

1
Department of Pharmaceutics, College of Pharmacy, University of Florida Gainesville, 32608 Florida, USA
2
Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, Ohio State University Columbus, 43210 Ohio, USA
3
College of Pharmacy and Wonkwang Oriental Medicines Research Institute, Wonkwang University, 54538 Iksan, Korea
4
Department of Surgery, University of Oklahoma Heath Science Center, 73104 Oklahoma, USA
5
Center for Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: George A. Calin
Non-Coding RNA 2017, 3(3), 24; https://doi.org/10.3390/ncrna3030024
Received: 21 July 2017 / Revised: 10 August 2017 / Accepted: 21 August 2017 / Published: 25 August 2017
A gene array was used to profile the expression of 22,875 long non-coding RNAs (lncRNAs) and a large number of protein coding genes in 47 specimens of pancreatic ductal adenocarcinoma (PDAC), adjacent benign pancreas and the pancreas from patients without pancreatic disease. Of the lncRNAs profiled, the expression of 126 were significantly increased and 260 were decreased in the tumors (p < 0.05, 2-fold). The expression of one lncRNA in particular, heterogeneous nuclear ribonucleoprotein U (HNRNPU) processed transcript (also known as ncRNA00201) was among the most significantly deregulated (increased four-fold) in the tumors compared to normal/adjacent benign tissues. Increased expression of HNRNPU processed transcript was associated with poor prognosis for patients with PDAC. The expression of HNRNPU processed transcript was increased in PDAC cell lines compared to noncancerous pancreatic cell lines. LNATM gapmer mediated inhibition of HNRNPU processed transcript reduced cell proliferation in Patu-T and PL45 pancreatic cancer cell lines. Reduced invasion and migration was reported upon HNRNPU processed transcript knockdown in Patu-T cells. Small interfering RNA (siRNA) knockdown of the HNRNPU protein coding gene correlated with a 55% reduction in the HNRNPU processed transcript expression and a corresponding reduction in proliferation of Patu-T and PL45 cells. However, gapmer inhibition of HNRNPU processed transcript did not affect HNRNPU mRNA levels. The lncRNA HNRNPU processed transcript expression is increased in both PDAC tissues and cell lines; knockdown of this lncRNA further reduces proliferation and invasion/migration of pancreatic carcinoma cells. View Full-Text
Keywords: pancreatic cancer; HNRNPU processed transcript; ncRNA00201; HNRNPU; lncRNA; LNATM gapmers pancreatic cancer; HNRNPU processed transcript; ncRNA00201; HNRNPU; lncRNA; LNATM gapmers
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Sutaria, D.S.; Jiang, J.; Azevedo-Pouly, A.C.P.; Lee, E.J.; Lerner, M.R.; Brackett, D.J.; Vandesompele, J.; Mestdagh, P.; Schmittgen, T.D. Expression Profiling Identifies the Noncoding Processed Transcript of HNRNPU with Proliferative Properties in Pancreatic Ductal Adenocarcinoma. Non-Coding RNA 2017, 3, 24.

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