Open Access

Comprehensive analysis of long non‑coding RNA‑messenger RNA‑microRNA co‑expression network identifies cell cycle‑related lncRNA in hepatocellular carcinoma

  • Authors:
    • Hai‑Rong Zhu
    • Xiang‑Nan Yu
    • Guang‑Cong Zhang
    • Xuan Shi
    • Enkhnaran Bilegsaikhan
    • Hong‑Ying Guo
    • Li‑Li Liu
    • Yu Cai
    • Guang‑Qi Song
    • Tao‑Tao Liu
    • Ling Dong
    • Harry L.A. Janssen
    • Shu‑Qiang Weng
    • Jian Wu
    • Xi‑Zhong Shen
    • Ji‑Min Zhu
  • View Affiliations

  • Published online on: August 23, 2019     https://doi.org/10.3892/ijmm.2019.4323
  • Pages: 1844-1854
  • Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding RNAs (lncRNAs) have been shown to contribute to progression and prognosis of hepatocellular carcinoma (HCC). However, expression profiling and interaction of lncRNAs with messenger RNAs (mRNAs) and microRNAs (miRNAs) remain largely unknown in HCC. The expression profiling of lncRNAs, mRNA and miRNAs was obtained using microarray. The Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to characterize potential functions of differentially expressed mRNAs. Cytoscape was applied to construct an lncRNA‑miRNA‑mRNA co‑expression network and candidate lncRNAs were validated via quantitative PCR in 30 pairs of HCC and adjacent tumor‑free tissues. In this study, 1,056 upregulated and 1,288 downregulated lncRNAs were identified, while 2,687 mRNAs and 6 miRNAs were aberrantly expressed in HCC compared with adjacent tumor‑free tissues. Potential functions of differentially expressed mRNAs were demonstrated to significantly participate in modulating critical genes in the cell cycle, such as cyclin E1 and cyclin B2. After screening, 95 lncRNAs, 5 miRNAs and 36 mRNAs were recruited for construction of lncRNA‑mRNA‑miRNA co‑expression network in the cell cycle pathway. Subsequently, the top 5 lncRNAs that potentially modulate critical genes in the cell cycle were selected as the candidates for further verification. Kaplan‑Meier curves using the Cancer Genome Atlas database showed that 13 targeted mRNAs were associated with overall survival of HCC patients. Finally, three lncRNAs, including ENST00000522221, lnc‑HACE1‑6:1 and lnc‑ICOSLG‑11:1, are significantly upregulated in HCC tissues compared with adjacent tumor‑free tissues. These findings suggest that lncRNAs play essential roles in the pathogenesis of HCC via regulating coding genes and miRNAs, and may be important targets for diagnosis and treatment of this disease.
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November-2019
Volume 44 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Copy and paste a formatted citation
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Spandidos Publications style
Zhu HR, Yu XN, Zhang GC, Shi X, Bilegsaikhan E, Guo HY, Liu LL, Cai Y, Song GQ, Liu TT, Liu TT, et al: Comprehensive analysis of long non‑coding RNA‑messenger RNA‑microRNA co‑expression network identifies cell cycle‑related lncRNA in hepatocellular carcinoma. Int J Mol Med 44: 1844-1854, 2019
APA
Zhu, H., Yu, X., Zhang, G., Shi, X., Bilegsaikhan, E., Guo, H. ... Zhu, J. (2019). Comprehensive analysis of long non‑coding RNA‑messenger RNA‑microRNA co‑expression network identifies cell cycle‑related lncRNA in hepatocellular carcinoma. International Journal of Molecular Medicine, 44, 1844-1854. https://doi.org/10.3892/ijmm.2019.4323
MLA
Zhu, H., Yu, X., Zhang, G., Shi, X., Bilegsaikhan, E., Guo, H., Liu, L., Cai, Y., Song, G., Liu, T., Dong, L., Janssen, H. L., Weng, S., Wu, J., Shen, X., Zhu, J."Comprehensive analysis of long non‑coding RNA‑messenger RNA‑microRNA co‑expression network identifies cell cycle‑related lncRNA in hepatocellular carcinoma". International Journal of Molecular Medicine 44.5 (2019): 1844-1854.
Chicago
Zhu, H., Yu, X., Zhang, G., Shi, X., Bilegsaikhan, E., Guo, H., Liu, L., Cai, Y., Song, G., Liu, T., Dong, L., Janssen, H. L., Weng, S., Wu, J., Shen, X., Zhu, J."Comprehensive analysis of long non‑coding RNA‑messenger RNA‑microRNA co‑expression network identifies cell cycle‑related lncRNA in hepatocellular carcinoma". International Journal of Molecular Medicine 44, no. 5 (2019): 1844-1854. https://doi.org/10.3892/ijmm.2019.4323