Expression Profiling Identifies the Noncoding Processed Transcript of HNRNPU with Proliferative Properties in Pancreatic Ductal Adenocarcinoma.
Dhruvitkumar S. Sutaria,Dhruvitkumar S. Sutaria,Jinmai Jiang,Ana Clara P. Azevedo-Pouly,Eun Joo Lee,Megan R. Lerner,Daniel J. Brackett,Jo Vandesompele,Pieter Mestdagh,Thomas D. Schmittgen +9 more
TLDR
The expression of HNRNPU processed transcript was increased in PDAC cell lines compared to noncancerous pancreatic cell lines; knockdown of this lncRNA further reduces proliferation and invasion/migration of pancreatic carcinoma cells.Abstract:
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.read more
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The implication of long non-coding RNAs in the diagnosis, pathogenesis and drug resistance of pancreatic ductal adenocarcinoma and their possible therapeutic potential.
TL;DR: The current review discusses the potential role and molecular mechanism of lncRNA in regulating the prominent hallmarks of cancer including abnormal growth, survival, metastasis, and drug-resistance in PDAC and highlights the possible application of various therapeutic strategies.
Journal ArticleDOI
lncRNA THAP9-AS1 Promotes Pancreatic Ductal Adenocarcinoma Growth and Leads to a Poor Clinical Outcome via Sponging miR-484 and Interacting with YAP.
Nan Li,Guohua Yang,Liyun Luo,Li Ling,Xiaorong Wang,Lejuan Shi,Junsong Lan,Xiaoting Jia,Qiong Zhang,Ze Long,Jinbao Liu,Weimin Hu,Zhimin He,Haiying Liu,Wanqing Liu,Guopei Zheng +15 more
TL;DR: It is demonstrated that lncRNA THAP9-AS1 is overexpressed in PDAC in multiple patient sample sets, which is significantly associated with poor outcome of patients with PDAC and may serve as a potential biomarker and therapeutic target for PDAC treatment.
Journal ArticleDOI
In Systemic Sclerosis, a Unique Long Non Coding RNA Regulates Genes and Pathways Involved in the Three Main Features of the Disease (Vasculopathy, Fibrosis and Autoimmunity) and in Carcinogenesis.
TL;DR: In SSc, the identification of a unique deregulated lncRNA that regulates genes involved in the three main features of the disease and in tumor-associated pathways, provides insight in disease pathogenesis and opens avenues for the design of novel therapeutic strategies.
Journal ArticleDOI
Identifying MMP14 and COL12A1 as a potential combination of prognostic biomarkers in pancreatic ductal adenocarcinoma using integrated bioinformatics analysis
Jingyi Ding,Yanxi Liu,Yu Lai +2 more
TL;DR: Findings indicated that FBN1 and COL8A1 appear to be involved in the progression of PDAC, and upregulation of MMP14 and COL12A1 is associated with poor overall survival, and these might be a combination of prognostic biomarkers in PDAC.
Journal ArticleDOI
Identification of potential hub genes associated with the pathogenesis and prognosis of pancreatic duct adenocarcinoma using bioinformatics meta-analysis of multi-platform datasets.
TL;DR: In this article, the authors analyzed gene expression profiles to reveal genes involved in the tumorigenesis of pancreatic duct adenocarcinoma (PDAC) using a Cox proportional hazards model.
References
More filters
Journal ArticleDOI
Controlling the false discovery rate: a practical and powerful approach to multiple testing
Yoav Benjamini,Yosef Hochberg +1 more
TL;DR: In this paper, a different approach to problems of multiple significance testing is presented, which calls for controlling the expected proportion of falsely rejected hypotheses -the false discovery rate, which is equivalent to the FWER when all hypotheses are true but is smaller otherwise.
Journal ArticleDOI
Cancer statistics, 2015.
TL;DR: The overall cancer death rate decreased from 215.1 (per 100,000 population) in 1991 to 168.7 in 2011, a total relative decline of 22%.
Journal ArticleDOI
Projecting Cancer Incidence and Deaths to 2030: The Unexpected Burden of Thyroid, Liver, and Pancreas Cancers in the United States
Lola Rahib,Benjamin Smith,Rhonda Aizenberg,Allison B. Rosenzweig,Julie M. Fleshman,Lynn M. Matrisian +5 more
TL;DR: Pancreas and liver cancers are projected to surpass breast, prostate, and colorectal cancers to become the second and third leading causes of cancer-related death by 2030, respectively.
Journal ArticleDOI
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Siân Jones,Xiaosong Zhang,D. Williams Parsons,D. Williams Parsons,Jimmy Lin,Rebecca J. Leary,Philipp Angenendt,Parminder Mankoo,Hannah Carter,Hirohiko Kamiyama,Antonio Jimeno,Seung-Mo Hong,Baojin Fu,Ming Tseh Lin,Eric S. Calhoun,Mihoko Kamiyama,Kimberly Walter,Tatiana Nikolskaya,Yuri Nikolsky,James Hartigan,Douglas Smith,Manuel Hidalgo,Steven D. Leach,Alison P. Klein,Elizabeth M. Jaffee,Michael Goggins,Anirban Maitra,Anirban Maitra,Christine A. Iacobuzio-Donahue,James R. Eshleman,Scott E. Kern,Ralph H. Hruban,Rachel Karchin,Nickolas Papadopoulos,Giovanni Parmigiani,Bert Vogelstein,Victor E. Velculescu,Kenneth W. Kinzler +37 more
TL;DR: It is found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations, which defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors.
Journal ArticleDOI
CPC: assess the protein-coding potential of transcripts using sequence features and support vector machine
TL;DR: A support vector machine-based classifier, named Coding Potential Calculator (CPC), to assess the protein-coding potential of a transcript based on six biologically meaningful sequence features, which can discriminate coding from noncoding transcripts with high accuracy.