Abstract
Since the new gene regulation involving competing endogenous RNA (ceRNA) interactions targeted by common microRNAs (miRNAs) was found, several computational methods have been proposed to derive ceRNA networks. However, most of the ceRNA networks are restricted to represent either miRNA-target RNA interactions or lncRNA-miRNA-mRNA interactions. From the extensive data analysis, we found that competition for miRNA-binding occurs not only between lncRNAs and mRNAs but also between lncRNAs or between mRNAs. Furthermore, a large number of pseudogenes also act as ceRNAs, thereby regulate other genes. In this study, we considered all lncRNAs, mRNAs and pseudogenes as potential ceRNAs and developed a method for constructing an integrative ceRNA network which includes all possible interactions of ceRNAs mediated by miRNAs: lncRNA-miRNA-mRNA, lncRNA-miRNA-lncRNA, lncRNA-miRNA-pseudogene, mRNA-miRNA-mRNA, mRNA-miRNA-pseudogene, and pseudogene-miRNA-pseudogene. We constructed integrative ceRNA networks for breast cancer, liver cancer and lung cancer, and derived several triplets of ceRNAs which can be used as potential prognostic biomarkers. The potential prognostic triplets could not be found when only lncRNA-miRNA-mRNA interactions were considered. Although preliminary, our approach to constructing integrative ceRNA networks is applicable to multiple types of cancer and will help us find potential prognostic biomarkers in cancer.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Wilusz, J.E., Sunwoo, H., Spector, D.L.: Long noncoding RNAs: functional surprises from the RNA world. Genes Dev. 23, 1494–1504 (2009)
Bartel, D.P.: Metazoan microRNAs. Cell 173, 20–51 (2018)
Lü, M.H., et al.: Long noncoding RNA BC032469, a novel competing endogenous RNA, upregulates hTERT expression by sponging miR-1207-5p and promotes proliferation in gastric cancer. Oncogene 35, 3524–3534 (2016)
Salmena, L., Poliseno, L., Tay, Y., Kats, L., Pandolfi, P.P.: A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146, 353–358 (2011)
Jiang, R., Zhao, C., Gao, B., Xu, J., Song, W., Shi, P.: Mixomics analysis of breast cancer: long non-coding RNA linc01561 acts as ceRNA involved in the progression of breast cancer. Int. J. Biochem. Cell Biol. 102, 1–9 (2018)
Zhu, Y., Bian, Y., Zhang, Q., et al.: Construction and analysis of dysregulated lncRNA-associated ceRNA network in colorectal cancer. J. Cell Biochem. 120, 9250–9263 (2019)
Poliseno, L., Salmena, L., Zhang, J., Carver, B., Haveman, W.J., Pandolfi, P.P.: A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465, 1033–1038 (2010)
Robinson, M.D., McCarthy, D.J., Smyth, G.K.: edgeR: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2010)
Huang, H.Y., et al.: miRTarBase 2020: updates to the experimentally validated microRNA-target interaction database. Nucleic Acids Res. 48, D148–D154 (2020)
Jeggari, A., Marks, D.S., Larsson, E.: miRcode: a map of putative microRNA target sites in the long non-coding transcriptome. Bioinformatics 28, 2062–2063 (2012)
Agarwal, V., Bell, G.W., Nam, J.-W., Bartel, D.P.: Predicting effective microRNA target sites in mammalian mRNAs. Elife 4, e05005 (2015)
Zhou, M., et al.: Characterization of long non-coding RNA-associated ceRNA network to reveal potential prognostic lncRNA biomarkers in human ovarian cancer. Oncotarget 7, 12598–12611 (2016)
Liu, H., et al.: Integrative analysis of dysregulated lncRNA-associated ceRNA network reveals functional lncRNAs in gastric cancer. Genes 9, 303 (2018)
Wasserman, S., Faust, K., Iacobucci, D., Granovetter, M.: Social Network Analysis: Methods and Applications. Cambridge University Press (1994)
Chen, E.Y., et al.: Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinf. 14, 128 (2013)
Zhou, W., Liu, T., Saren, G., Liao, L., Fang, W., Zhao, H.: Comprehensive analysis of differentially expressed long non-coding RNAs in non-small cell lung cancer. Oncol. Lett. 18, 1145–1156 (2019)
Wang, S.M., Ooi, L.L., Hui, K.M.: Upregulation of Rac GTPase-activating protein 1 is significantly associated with the early recurrence of human hepatocellular carcinoma. Clin. Cancer Res. 17, 6040–6051 (2011)
Saigusa, S., et al.: Clinical significance of RacGAP1 expression at the invasive front of gastric cancer. Gastric Cancer 18, 84–92 (2015)
Imaoka, H., et al.: RacGAP1 expression, increasing tumor malignant potential, as a predictive biomarker for lymph node metastasis and poor prognosis in colorectal cancer. Carcinogenesis 36, 346–354 (2015)
Zhang, X., Ma, N., Yao, W., Li, S., Ren, Z.: RAD51 is a potential marker for prognosis and regulates cell proliferation in pancreatic cancer. Cancer Cell Int. 19, 356 (2019)
Nowacka-Zawisza, M., et al.: RAD51 and XRCC3 polymorphisms are associated with increased risk of prostate cancer. J. Oncol. 2019, 2976373 (2019)
Du, S., et al.: Long non-coding RNA MAGI2-AS3 inhibits breast cancer cell migration and invasion via sponging microRNA-374a. Cancer Biomarkers Sect. A Dis. markers 24, 269–277 (2019)
Tang, H., et al.: miR-200b and miR-200c as prognostic factors and mediators of gastric cancer cell progression. Clin. Cancer Res. Official J. Am. Assoc. Cancer Res. 19, 5602–5612 (2013)
Liu, X.G., et al.: High expression of serum miR-21 and tumor miR-200c associated with poor prognosis in patients with lung cancer. Med. Oncol. (Northwood, London, England) 29, 618–626 (2012)
Liu, C., et al.: The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat. Med. 17, 211–215 (2011)
Li, N., et al.: miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett. 275, 44–53 (2009)
Mishan, M.A., Tabari, M.A.K., Parnian, J., Fallahi, J., Mahrooz, A., Bagheri, A.: Functional mechanisms of miR-192 family in cancer. Genes Chromosom. Cancer 59(12), 722–735 (2020)
Hoeijmakers, J.H.: DNA damage, aging, and cancer. N. Engl. J. Med. 361, 1475–1485 (2009)
Acknowledgements
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (NRF-2020R1A2B5B01096299, NRF-2018K2A9A2A11080914).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Nature Switzerland AG
About this paper
Cite this paper
Lee, S., Lee, W., Ren, S., Han, K. (2021). A Method for Constructing an Integrative Network of Competing Endogenous RNAs. In: Huang, DS., Jo, KH., Li, J., Gribova, V., Premaratne, P. (eds) Intelligent Computing Theories and Application. ICIC 2021. Lecture Notes in Computer Science(), vol 12838. Springer, Cham. https://doi.org/10.1007/978-3-030-84532-2_37
Download citation
DOI: https://doi.org/10.1007/978-3-030-84532-2_37
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-84531-5
Online ISBN: 978-3-030-84532-2
eBook Packages: Computer ScienceComputer Science (R0)