Genome‐wide identification of a competing endogenous RNA network in cholangiocarcinoma

Abstract

Cholangiocarcinoma (CCA) is the second widespread liver tumor with relatively poor survival. Increasing evidence in recent studies showed long noncoding RNAs (lncRNAs) exert a crucial impact on the development and progression of CCA based on the mechanism of competing endogenous RNAs (ceRNAs). However, functional roles and regulatory mechanisms of lncRNA‐regulated ceRNA in CCA, are only partially understood. The expression profile of messenger RNAs (mRNAs), lncRNAs, and microRNAs (miRNAs) downloaded from The Cancer Genome Atlas were comprehensively investigated. Differential expression of these three types of RNA between CCA and corresponding precancerous tissues were screened out for further analysis. On the basis of interactive information generated from miRDB, miRTarBase, TargetScan, and miRcode public databases, we then constructed an mRNA‐miRNA‐lncRNA regulatory network. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses were conducted to identify the biological function of the ceRNA network involved in CCA. As a result, 2883 mRNAs, 136 miRNAs, and 993 lncRNAs were screened out as differentially expressed RNAs in CCA. In addition, a ceRNA network in CCA was constructed, composing of 50 up and 27 downregulated lncRNAs, 14 up and 7 downregulated miRNAs, 29 up and 25 downregulated mRNAs. Finally, gene set enrichment and pathway analysis indicated our CCA‐specific ceRNA network was related with cancer‐related pathway and molecular function. In conclusion, our research identified a novel lncRNA‐related ceRNA network in CCA, which might act as a potential therapeutic target for patients with CCA.

Long non-coding RNA LINC00665 promotes gemcitabine resistance of Cholangiocarcinoma cells via regulating EMT and stemness properties through miR-424-5p/BCL9L axis

“…1C). Previous transcriptomesequencing studies also indicated that LINC00665 was overexpressed in tumor tissues of CCA patients 13,14,23 , Fig. 1 LINC00665 is upregulated and associated with poor prognosis and chemoresistance in CCA patients.…”

“…1C ). Previous transcriptome-sequencing studies also indicated that LINC00665 was overexpressed in tumor tissues of CCA patients 13 , 14 , 23 , thus we further checked the expression of LINC00665 in 100 pairs of CCA samples and matched adjacent-normal tissues collected from Henan Provincial People’s Hospital. Our results revealed that LINC00665 was significantly upregulated in CCA patients, corresponding with previous results (Fig.…”

“…Long intergenic non-protein coding RNA 665 (LINC00665) is a lncRNA located in chromosome 19, and recent studies indicate that LINC00665 is dysregulated and enrolled in the tumorigenesis and chemoresistance in a variety of cancers 11 , 12 . Moreover, transcriptome sequencing studies of cholangiocarcinoma patients reveal that LINC00665 is upregulated in cholangiocarcinoma tissues, but the exact role of this lncRNA is uncertain 13 , 14 .…”

Concise Review: Functional Roles and Therapeutic Potentials of Long Non-coding RNAs in Cholangiopathies

“…lncRNAs function as competing endogenous RNAs (ceRNAs), which interrupt miRNA functions and alter protein expression, and this may be a characteristic hallmark in CCA. Genome-wide data analysis or RNA-Seq profiling identified various lncRNAs and ceRNA networks associated with CCA, and some candidate lncRNAs are significantly associated with survival rates (40)(41)(42). Recent studies have identified a number of lncRNAs that are associated with CCA progression and invasion.…”

Long noncoding RNA NNT-AS1 enhances the malignant phenotype of bladder cancer by acting as a competing endogenous RNA on microRNA-496 thereby increasing HMGB1 expression

“…We found that NNT-AS1 is mainly located in the cytoplasm of T24 and TCC-SUP cells ( Figure 3A). Growing evidence suggests that cytoplasmic lncRNAs can function as ceRNAs by competitively interacting with specific miRNAs [43][44][45]. A bioinformatic algorithm, starBase 3.0, was executed to search for a potential miRNA target of NNT-AS1.…”