4.6 Article

Construction and Investigation of a lncRNA-Associated ceRNA Regulatory Network in Cholangiocarcinoma

Journal

FRONTIERS IN ONCOLOGY
Volume 9, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2019.00649

Keywords

competing endogenous RNA network; long non-coding RNA; cholangiocarcinoma; prognosis microRNA

Categories

Funding

  1. International Science and Technology Cooperation Projects [2016YFE0107100]
  2. Capital Special Research Project for Health Development [2014-2-4012]
  3. Beijing Natural Science Foundation [L172055, 7192158]
  4. National Ten Thousand Talent Program
  5. Fundamental Research Funds for the Central Universities [3332018032]
  6. CAMS Innovation Fund for Medical Science (CIFMS) [2017-I2M-4-003, 2018-I2M-3-001]

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Background/Aims: As a type of malignant tumor commonly found in the bile duct, cholangiocarcinoma (CCA) has a poor prognosis. Long non-coding RNA (lncRNA) has recently drawn increasing attention because it functions as a competing endogenous RNA (ceRNA) to hinder miRNA functions that participate in posttranscriptional regulatory networks in tumors. Therefore, to investigate the mechanisms of CCA carcinogenesis and to enhance treatment efficiency, the expression profiles, including lncRNA, miRNA, and mRNA data, were comprehensively integrated and analyzed in this study. Methods: A comprehensive comparison was performed on the RNA-sequencing and miRNA profiles data of 36 CCA samples and 9 normal samples from The Cancer Genome Atlas (TOGA) database. Then, a dysregulated lncRNA-related ceRNA network was established by using four public databases. Results: In summary, 1,410 lncRNAs, 64 miRNAs, and 3,494 mRNAs appeared as genes that were aberrantly expressed in CCA. Then, a dysregulated ceRNA network related to the lncRNAs was constructed. The network included 116 lncRNAs, 13 miRNAs and 60 mRNAs specific to CCA. The survival analysis showed that, among them, 26 lncRNAs, 3 miRNAs, and 13 mRNAs were prognostic biomarkers for patients with CCA. Finally, three mRNAs were selected for validation of their expression levels in the Gene Expression Omnibus (GEO) database. The results indicated that the expression of those genes was highly consistent between the TOGA and GEO databases. Conclusions: The findings in this study provide a better understanding of the ceRNA network involved in CCA biology and lay a solid foundation for improving CCA diagnosis and prognosis.

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