Global identification and characterization of lncRNAs that control inflammation in malignant cholangiocytes

Abstract

BackgroundLong noncoding RNAs (lncRNAs) are known to play important roles in different cell contexts, including cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis, and associated with chronic inflammation and damage to the biliary epithelium. This study determined whether lncRNAs were dysregulated and participated in disease diagnosis or pivotal inflammation pathways through a genome-wide lncRNA screening and functional analysis.ResultsWe firstly identified a large number of lncRNAs abnormally expressed between 9 pairs of cancerous and adjacent tissues of CCA, and between intra-hepatic CCA and extra-hepatic CCA through a genome-wide profiling. A set of aberrant differentially expressed lncRNAs were further validated in a training set (16 pairs) and a test set (11 pairs) of CCA patient samples. Following assessment of the diagnostic value of the 7 differentially expressed lncRNAs, we confirmed the optimal combination of H19, C3P1, AC005550.3, PVT1, and LPAL2 with area under the curve of 0.8828 [95% CI: 0.7441–1.021, P < 0.001], with 93.75% sensitivity and 81.25% specificity, at the cutoff point of − 0.2884 to distinguish the CCA tissue from the normal ones, suggesting that specific lncRNAs may have potential for detecting CCA. More importantly, the genome-wide locus and lncRNA/mRNA co-expression analyses revealed a set of lncRNAs that participated in inflammation and oxidative stress response pathways by regulating genes in cis or in trans. Finally, APOC1P1, PVT1, and LPAL2 were validated to regulate the migration and some pivotal inflammation genes under the CCA pathogenesis.ConclusionsOur findings are the first to show that lncRNAs may not only be potential biomarkers of CCA progression but also respond to inflammation in CCA.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5133-8) contains supplementary material, which is available to authorized users.

CeRNA Network Analysis Representing Characteristics of Different Tumor Environments Based on 1p/19q Codeletion in Oligodendrogliomas

“…In addition, in the results of an expanded study on lower grade glioma, more statistically significant genes were found. There were reports with findings consistent with those of ours on hsa-miR-1262, hsa-miR-455-3p, LPAL2 [83][84][85][86], and some reports even contradicted our findings on hsa-miR-204-5p and hsa-miR-197-3p [87,88]. Although related studies are still insufficient, the previous report about hsa-miR-186-5p in glioblastoma contradicted our findings [89].…”

Apolipoprotein C1: Its Pleiotropic Effects in Lipid Metabolism and Beyond

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Expression of long non-coding RNA ANRIL predicts a poor prognosis in intrahepatic cholangiocarcinoma

“…Mechanistically, co-expression network analysis of coding and non-coding RNA in resected CCA tumors identified lncRNA (e.g. APOC1P1, PVT1) possibly regulating inflammation and oxidative stress in malignant cholangiocytes 10,11 . Notably, pvt1 oncogene (PVT1) was shown to promote cell proliferation and migration by epigenetically silencing angiopoietin like 4 (ANGPTL4), a tumor suppressor gene candidate 12 .…”