Genome-Wide Analysis Identified a Number of Dysregulated Long Noncoding RNA (lncRNA) in Human Pancreatic Ductal Adenocarcinoma

Abstract

Background:Long noncoding RNAs have been shown to play crucial roles in cancer biology, while the long noncoding RNA landscapes of pancreatic ductal adenocarcinoma have not been completely characterized. We aimed to determine whether long noncoding RNA could serve as early diagnostic biomarkers for pancreatic ductal adenocarcinoma.Method:We conducted a genome-wide microarray analysis on pancreatic ductal adenocarcinoma and their adjacent noncancerous tissues from 8 Chinese patients.Results:A total of 3352 significantly differentially expressed long noncoding RNAs were detected. Of total, 1249 long noncoding RNAs were upregulated and 2103 were downregulated (fold change ≥2, P < 0.05, FDR <0.05). These differentially expressed long noncoding RNAs were not evenly distributed among chromosomes in human genome. Hierarchical clustering of these differentially expressed long noncoding RNAs revealed large variabilities in long noncoding RNA expression among individual patient, indicating that certain long noncoding RNAs could play a unique role or be used as a biomarker for specific subtype of pancreatic ductal adenocarcinoma. Gene Ontology enrichment and pathway analysis identified several remarkably dysregulated pathways in pancreatic ductal adenocarcinoma tissue, such as interferon-γ-mediated signaling pathway, mitotic cell cycle and proliferation, extracellular matrix receptor interaction, focal adhesion, and regulation of actin cytoskeleton. The co-expression network analysis detected 393 potential interactions between 80 differentially expressed long noncoding RNAs and 105 messenger RNAs. We experimentally verified 7 most markedly dysregulated long noncoding RNAs from the network.Conclusion:Our study provided a genome-wide survey of dysregulated long noncoding RNAs and long noncoding RNA/messenger RNA co-regulation networks in pancreatic ductal adenocarcinoma tissue. These dysregulated long noncoding RNA/messenger RNA networks could be used as biomarkers to provide early diagnosis of pancreatic ductal adenocarcinoma or its subtype, predict prognosis, and evaluate treatment efficacy.

A Systems-Level Analysis Reveals Circadian Regulation of Splicing in Colorectal Cancer

“…ADGRE5 , EDN1 , and STXBP6 are all involved in cell-cell adhesion [ [58] , [59] , [60] ], while EPN2 is involved in clathrin-mediated endocytosis and acts as a suppressor of VEGF-mediated angiogenesis [ 61 ]. The non-coding RNA genes TPRXL and SH3PXD2A-AS1 have both been linked to cancer as well [ 62 , 63 ].…”

Long non‑coding RNA H19 knockdown inhibits the cell viability and promotes apoptosis of thyroid cancer cells through regulating the PI3K/AKT pathway

“…Long non-coding RNAs (lncRNAs) are a class of non-protein-coding transcripts that are >200 nucleotides in length (5). Increasing evidence indicates that lncRNAs are crucial factors in tissue physiology and the pathological processes of various diseases, including cancer (6,7). A large number of dysregulated lncRNAs have been identified in cancer, suggesting their oncogenic or tumor-suppressive properties (8,9).…”

Upregulation of LncRNA PVT1 Facilitates Pancreatic Ductal Adenocarcinoma Cell Progression and Glycolysis by Regulating MiR-519d-3p and HIF-1A

“…Recurrent translocations of PVT1 that arise through chromothripsis, such as PVT1-MYC and PVT1-NDRG1, often occur in malignant tumor [18]. Correlation analysis further revealed that the majority of lncRNA and mRNAs were negatively correlated, suggesting that lncRNAs were likely to serve as negative regulators of their targeting coding genes in PDAC tissues [19]. In addition, recent reports showed that PVT1 can be as a competing endogenous RNA to sponge miRNAs to governs cancer characters [6], [9], [20], [23].…”