Research Paper Volume 12, Issue 22 pp 23251—23274

Comprehensive circular RNA expression profiling constructs a ceRNA network and identifies hsa_circ_0000673 as a novel oncogene in distal cholangiocarcinoma

Xin Zhao1, *, , Xinxue Zhang1, *, , Zhigang Zhang2, , Zhe Liu1, , Jiqiao Zhu1, , Shaocheng Lyu1, , Lixin Li1, , Ren Lang1, , Qiang He1, ,

  • 1 Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated with Capital Medical University, Beijing, China
  • 2 School of Information Management and Statistics, Hubei University of Economics, Wuhan, Hubei Province, China
* Equal contribution

Received: February 26, 2020       Accepted: September 4, 2020       Published: November 18, 2020
How to Cite

Copyright: © 2020 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Circular RNAs (circRNAs) play an important role in cholangiocarcinoma (CCA) development; however, the expression and functions of circRNAs in distal CCA (dCCA) remain unknown. Herein, we explored the expression profile of circRNAs in six paired dCCA tumor and adjacent normal tissue samples using microarray. A total of 171 differentially expressed (DE) circRNAs were identified in dCCA tissues. Host genes of DE circRNAs were enriched in the cellular cytoskeleton and adheren junction. Bioinformatics analyses were used to establish a circRNA-microRNA-mRNA network for dCCA. Protein-protein interaction networks were constructed, and five hub genes were associated with the regulation of the cell cycle based on gene set enrichment analyses. Five DE circRNAs were validated with qRT-PCR in 40 pairs of dCCA tissues, and hsa_circ_0000673 showed promising diagnostic performance in distinguishing dCCA from normal tissues (AUC = 0.85, p < 0.01). Overexpression of hsa_circ_0000673 was associated with tumor invasion (p = 0.001), poor differentiation (p = 0.041), and residual tumor (p = 0.044). In vitro experiments indicated that inhibition of hsa_circ_0000673 suppressed the proliferation, migration, and invasion of CCA cells. This research provided a landscape of dysregulated circRNAs in dCCA and identified hsa_circ_0000673 as a potential biomarker and therapeutic target for dCCA.


dCCA: distal cholangiocarcinoma; CCA: cholangiocarcinoma; circRNA: circular RNA; miRNA: microRNA; PPIs: protein-protein interactions; DE: differentially expressed; HCC: hepatocellular carcinoma; ceRNAs: competing endogenous RNAs; log2FC: log2(fold change); GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Gene and Genomes; qRT-PCR: quantitative real-time polymerase chain reaction; CSCD: Cancer-Specific CircRNA Database; GSEA: gene set enrichment analysis; ROC curve: receiver operating characteristic curve; AUC: area under the curve; siRNA: small interfering RNA; CCK-8: cell counting kit-8; AJCC: American Joint Committee on Cancer; TCGA: The Cancer Genome Atlas; MCODE: Molecular Complex Detection; GEO: Gene Expression Omnibus; STRING: Search Tool for the Retrieval of Interacting Genes; SiRNA: small interfering RNA.