The diagnostic/prognostic potential and molecular functions of long non-coding RNAs in the exosomes derived from the bile of human cholangiocarcinoma

Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy associated with unfavorable prognosis, and it’s difficult to diagnose and no effective treatments are available. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and metastasis. Intact lncRNAs from exosomes have sparked much interest as potential biomarker for the non-invasive analysis of disease. Here, via exosome sequencing on lncRNAs, GO analysis, KEGG pathway and co-expression analysis, receiver operating characteristic curve and survival analyses, we found that, compared with control group, lncRNAs of ENST00000588480.1 and ENST00000517758.1 showed significantly increased expressions in CCA group. Moreover, area under the curve (AUC) was increased to 0.709 when combined the two lncRNAs, they had a sensitivity and specificity of 82.9% and 58.9% respectively. Further, the higher levels of the two lncRNAs showed a significantly increasing trend with the advancement of cancer TNM stages, and prognosticated a poor survival. In addition, KEGG pathway analysis showed that the most significant difference term was “p53 signaling pathway” (KEGG ID: hsa04115, p: 0.001). The altered lncRNAs and their target genes were included to reconstruct a co-expression network. These altered lncRNAs were mainly related to cellular processes, environmental information processing and organismal systems, etc. Collectively, our findings provided the potential roles of lncRNAs of ENST00000588480.1 and ENST00000517758.1 in CCA, and implicated these lncRNAs as potential diagnostic and therapeutic targets for CCA.

Long noncoding‐RNA component of mitochondrial RNA processing endoribonuclease is involved in the progression of cholangiocarcinoma by regulating microRNA‐217

“…Our previous study showed differentially expressed lncRNAs in exosomes derived from bile of CCA patients . To investigate whether the indicated lncRNAs previously sequenced and verified in CCA bile exosomes were differentially expressed in CCA tissues, we first used qRT‐PCR to detect and compare the expression levels of 10 lncRNAs in CCA and adjacent tissues.…”

“…Our previous study showed differentially expressed lncRNAs in exosomes derived from bile of CCA patients. 8 To investigate whether the indicated lncRNAs previously sequenced and verified in CCA bile exosomes were differentially expressed in CCA tissues, we first used qRT-PCR to detect and compare the expression levels of 10 lncRNAs in CCA and adjacent tissues. Results showed that expressions of ENST00000601661.1, NR_003051 and ENST00000516869.1 in CCA tissues were significantly higher than those in adjacent tissues compared to the other seven lncR-NAs (Figure 1, A1-A10).…”

“…However, there is still little knowledge about lncRNAs in CCA as a result of unavailability of CCA tissues. Our previous studies on CCA bile‐derived exosomes showed that the dysregulated lncRNAs may serve as molecular markers for the diagnosis of CCA . Nevertheless, their expression in CCA tissues and their role in the progression of CCA are not yet clear.…”

Extracellular Vesicles in Liver Diseases: Meeting Report from the International Liver Congress 2018

“…Up‐regulation of an miR panel (i.e., 191, 486‐3p, 1274b, 16, 484) was described in bile EVs from patients with CCA compared to control individuals (i.e., patients with PSC, a known risk factor for CCA, biliary obstruction, or bile leak syndrome) with diagnostic significance (SEN, 67%; SPE, 96%) . In addition, two lncRNAs (ENST00000588480.1 and ENST00000517758.1) were reported up‐regulated in bile EVs from patients with CCA compared to biliary obstruction conditions (SEN, 83%; SPE, 59%; area under the receiver operating characteristic curve [AUROC], 0.709) …”

The Advancement of Long Non-Coding RNAs in Cholangiocarcinoma Development

“…These lncRNAs may promote proliferation, migration and invasion of CCA cells including lncRNA AFAP1-AS1, ASAP1-IT1, CCAT1, CCAT2, H19, HULC, LINC01296, ENST0000058480.1, ENST00000517758.1, MALAT1, NEAT1, PANDAR, SNHG1, Sox2ot, SPRY4-IT1, TP73-AS1 etc. [23,29,30,[34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49]. In ICC, LncRNA CPS1-IT1 and TLINC are highly expressed [33,50].…”