Comprehensive analysis of the lncRNA-associated competing endogenous RNA network in breast cancer

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Abstract

Long noncoding RNAs (lncRNAs) have been confirmed to be potential prognostic markers in a variety of cancers and to interact with microRNAs (miRNAs) as competing endogenous RNAs (ceRNAs) to regulate target gene expression. However, the role of lncRNA-mediated ceRNAs in breast cancer (BC) remains unclear. In the present study, a ceRNA network was generated to explore their role in BC. The expression profiles of mRNAs, miRNAs and lncRNAs in 1,109 BC tissues and 113 normal breast tissues were obtained from The Cancer Genome Atlas database (TCGA). A total of 3,198 differentially expressed (DE) mRNAs, 150 differentially DEmiRNAs and 1,043 DElncRNAs were identified between BC and normal tissues. A lncRNA-miRNA-mRNA network associated with BC was successfully constructed based on the combined data obtained from RNA databases, and comprised 97 lncRNA nodes, 24 miRNA nodes and 74 mRNA nodes. The biological functions of the 74 DEmRNAs were further investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The results demonstrated that the DEmRNAs were significantly enriched in two GO biological process categories; the main biological process enriched term was ‘positive regulation of GTPase activity’. By KEGG analysis, four key enriched pathways were obtained, including the ‘MAPK signaling pathway’, the ‘Ras signaling pathway’, ‘prostate cancer’, and the ‘FoxO signaling pathway’. Kaplan-Meier survival analysis revealed that six DElncRNAs (INC AC112721.1, LINC00536, MIR7-3HG, ADAMTS9-AS1, AL356479.1 and LINC00466), nine DEmRNAs (KPNA2, RACGAP1, SHCBP1, ZNF367, NTRK2, ORS1, PTGS2, RASGRP1 and SFRP1) and two DEmiRNAs (hsa-miR-301b and hsa-miR-204) had significant effects on overall survival in BC. The present results demonstrated the aberrant expression of INC AC112721.1, AL356479.1, LINC00466 and MIR7-3HG in BC, indicating their potential prognostic role in patients with BC.

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miRDB: an online resource for microRNA target prediction and functional annotations

Nathan C. Wong, Xiaowei Wang (2014)

MicroRNAs (miRNAs) are small non-coding RNAs that are extensively involved in many physiological and disease processes. One major challenge in miRNA studies is the identification of genes regulated by miRNAs. To this end, we have developed an online resource, miRDB (http://mirdb.org), for miRNA target prediction and functional annotations. Here, we describe recently updated features of miRDB, including 2.1 million predicted gene targets regulated by 6709 miRNAs. In addition to presenting precompiled prediction data, a new feature is the web server interface that allows submission of user-provided sequences for miRNA target prediction. In this way, users have the flexibility to study any custom miRNAs or target genes of interest. Another major update of miRDB is related to functional miRNA annotations. Although thousands of miRNAs have been identified, many of the reported miRNAs are not likely to play active functional roles or may even have been falsely identified as miRNAs from high-throughput studies. To address this issue, we have performed combined computational analyses and literature mining, and identified 568 and 452 functional miRNAs in humans and mice, respectively. These miRNAs, as well as associated functional annotations, are presented in the FuncMir Collection in miRDB.

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The evolution of lncRNA repertoires and expression patterns in tetrapods.

Anamaria Necsulea, Magali Soumillon, Maria Warnefors … (2014)

Only a very small fraction of long noncoding RNAs (lncRNAs) are well characterized. The evolutionary history of lncRNAs can provide insights into their functionality, but the absence of lncRNA annotations in non-model organisms has precluded comparative analyses. Here we present a large-scale evolutionary study of lncRNA repertoires and expression patterns, in 11 tetrapod species. We identify approximately 11,000 primate-specific lncRNAs and 2,500 highly conserved lncRNAs, including approximately 400 genes that are likely to have originated more than 300 million years ago. We find that lncRNAs, in particular ancient ones, are in general actively regulated and may function predominantly in embryonic development. Most lncRNAs evolve rapidly in terms of sequence and expression levels, but tissue specificities are often conserved. We compared expression patterns of homologous lncRNA and protein-coding families across tetrapods to reconstruct an evolutionarily conserved co-expression network. This network suggests potential functions for lncRNAs in fundamental processes such as spermatogenesis and synaptic transmission, but also in more specific mechanisms such as placenta development through microRNA production.

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miR-155 gene: a typical multifunctional microRNA.

Isabella Faraoni, Francesca Romana Antonetti, John Cardone … (2009)

In the last years small RNA molecules, i.e. microRNA (miRNA) encoded by miR genes, have been found to play a crucial role in regulating gene expression of a considerable part of plant's and animal's genome. Here, we report the essential information on biogenesis of miRNAs and recent evidence on their important role in human diseases. Emphasis has been given to miR-155, since this molecule represents a typical multifunctional miRNA. Recent data indicate that miR-155 has distinct expression profiles and plays a crucial role in various physiological and pathological processes such as haematopoietic lineage differentiation, immunity, inflammation, cancer, and cardiovascular diseases. Moreover, miR-155 has been found to be implicated in viral infections, particularly in those caused by DNA viruses. The available experimental evidence indicating that miR-155 is over expressed in a variety of malignant tumors allows us to include this miRNA in the list of genes of paramount importance in cancer diagnosis and prognosis. Exogenous molecular control in vivo of miR-155 expression could open up new ways to restrain malignant growth and viral infections, or to attenuate the progression of cardiovascular diseases.

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Author and article information

Journal

Journal ID (nlm-ta): Oncol Rep

Journal ID (iso-abbrev): Oncol. Rep

Title: Oncology Reports

Publisher: D.A. Spandidos

ISSN (Print): 1021-335X

ISSN (Electronic): 1791-2431

Publication date (Print): December 2019

Publication date (Electronic): 15 October 2019

Publication date PMC-release: 15 October 2019

Volume: 42

Issue: 6

Pages: 2572-2582

Affiliations

[1 ]Department of Oncology, Taizhou Hospital of Traditional Chinese Medicine, Taizhou, Jiangsu 225300, P.R. China

[2 ]Department of General Practice, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215001, P.R. China

[3 ]Department of Intervention and Vascular Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215001, P.R. China

[4 ]Department of Oncology, Binzhou People's Hospital, Binzhou, Shandong 256600, P.R. China

[5 ]Department of Oncology, Jining Cancer Hospital, Jining, Shandong 272000, P.R. China

[6 ]Department of Radio-Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215001, P.R. China

Author notes

Correspondence to: Dr Min Huang, Department of General Practice, The Affiliated Suzhou Hospital of Nanjing Medical University, 26 Daoqian Street, Suzhou, Jiangsu 215001, P.R. China, E-mail: cxy442941186@ 123456163.com

Dr Wen-Jie Wang, Department of Radio-Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, 26 Daoqian Street, Suzhou, Jiangsu 215001, P.R. China, E-mail: doctor.wjwang@ 123456gmail.com

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Article

Publisher ID: OR-0-0-7374

DOI: 10.3892/or.2019.7374

PMC ID: 6826329

PubMed ID: 31638237

SO-VID: f1461f4d-c7e5-4c3d-b5b2-3e89ac74f8ad

License:

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

History

Date received : 29 December 2018

Date accepted : 19 September 2019

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Comprehensive analysis of the lncRNA-associated competing endogenous RNA network in breast cancer

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Abstract

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Karger: Oncology

Most cited references 60

miRDB: an online resource for microRNA target prediction and functional annotations

The evolution of lncRNA repertoires and expression patterns in tetrapods.

miR-155 gene: a typical multifunctional microRNA.

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