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      Comprehensive Analysis of Survival-Related lncRNAs, miRNAs, and mRNAs Forming a Competing Endogenous RNA Network in Gastric Cancer

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          Abstract

          To analyze and construct a survival-related endogenous RNA (ceRNA) network in gastric cancer (GC) with lymph node metastasis, we obtained expression profiles of long non-coding RNAs (lncRNAs), mRNAs, and microRNAs (miRNAs) in GC from The Cancer Genome Atlas database. The edgeR package was used to screen differentially expressed lncRNAs, mRNAs, and miRNAs between GC patients with lymphatic metastasis and those without lymphatic metastasis. Then, we used univariate Cox regression analysis to identify survival-related differentially expressed RNAs. In addition, we used multivariate Cox regression analysis to screen lncRNAs, miRNAs, and mRNAs for use in the prognostic prediction models. The results showed that 2,247 lncRNAs, 155 miRNAs, and 1,253 mRNAs were differentially expressed between the two patient groups. Using univariate Cox regression analysis, we found that 395 lncRNAs, eight miRNAs, and 180 mRNAs were significantly related to the survival time of GC patients. We next created a survival-related network consisting of 59 lncRNAs, seven miRNAs, and 36 mRNAs. In addition, we identified eight RNAs associated with prognosis by multivariate Cox regression analysis, comprising three lncRNAs (AC094104.2, AC010457.1, and AC091832.1), two miRNAs (miR-653-5p and miR-3923), and three mRNAs (C5orf46, EPHA8, and HPR); these were used to construct the prognostic prediction models, and their risk scores could be used to assess GC patients’ prognosis. In conclusion, this study provides new insights into ceRNA networks in GC and the screening of prognostic biomarkers for GC.

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          Most cited references44

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          A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?

          Here, we present a unifying hypothesis about how messenger RNAs, transcribed pseudogenes, and long noncoding RNAs "talk" to each other using microRNA response elements (MREs) as letters of a new language. We propose that this "competing endogenous RNA" (ceRNA) activity forms a large-scale regulatory network across the transcriptome, greatly expanding the functional genetic information in the human genome and playing important roles in pathological conditions, such as cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Endogenous microRNA sponges: evidence and controversy.

            The competitive endogenous RNA (ceRNA) hypothesis proposes that transcripts with shared microRNA (miRNA) binding sites compete for post-transcriptional control. This hypothesis has gained substantial attention as a unifying function for long non-coding RNAs, pseudogene transcripts and circular RNAs, as well as an alternative function for messenger RNAs. Empirical evidence supporting the hypothesis is accumulating but not without attracting scepticism. Recent studies that model transcriptome-wide binding-site abundance suggest that physiological changes in expression of most individual transcripts will not compromise miRNA activity. In this Review, we critically evaluate the evidence for and against the ceRNA hypothesis to assess the impact of endogenous miRNA-sponge interactions.
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              Long Non-Coding RNA in the Pathogenesis of Cancers

              The incidence and mortality rate of cancer has been quickly increasing in the past decades. At present, cancer has become the leading cause of death worldwide. Most of the cancers cannot be effectively diagnosed at the early stage. Although there are multiple therapeutic treatments, including surgery, radiotherapy, chemotherapy, and targeted drugs, their effectiveness is still limited. The overall survival rate of malignant cancers is still low. It is necessary to further study the mechanisms for malignant cancers, and explore new biomarkers and targets that are more sensitive and effective for early diagnosis, treatment, and prognosis of cancers than traditional biomarkers and methods. Long non-coding RNAs (lncRNAs) are a class of RNA transcripts with a length greater than 200 nucleotides. Generally, lncRNAs are not capable of encoding proteins or peptides. LncRNAs exert diverse biological functions by regulating gene expressions and functions at transcriptional, translational, and post-translational levels. In the past decade, it has been demonstrated that the dysregulated lncRNA profile is widely involved in the pathogenesis of many diseases, including cancer, metabolic disorders, and cardiovascular diseases. In particular, lncRNAs have been revealed to play an important role in tumor growth and metastasis. Many lncRNAs have been shown to be potential biomarkers and targets for the diagnosis and treatment of cancers. This review aims to briefly discuss the latest findings regarding the roles and mechanisms of some important lncRNAs in the pathogenesis of certain malignant cancers, including lung, breast, liver, and colorectal cancers, as well as hematological malignancies and neuroblastoma.
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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                02 March 2021
                2021
                : 12
                : 610501
                Affiliations
                [1] 1School of Public Health, Qingdao University , Qingdao, China
                [2] 2Department of Blood Transfusion, The Affiliated Hospital of Qingdao University, Qingdao University , Qingdao, China
                Author notes

                Edited by: Daniele Vergara, University of Salento, Italy

                Reviewed by: Kyoung-Mee Kim, Sungkyunkwan University, South Korea; Marina Damato, University of Salento, Italy

                *Correspondence: Yuxin Zheng, yxzheng@ 123456qdu.edu.cn

                These authors have contributed equally to this work

                This article was submitted to Cancer Genetics, a section of the journal Frontiers in Genetics

                Article
                10.3389/fgene.2021.610501
                7960915
                9ead10b2-f891-4d9b-b06b-056606c1ec4b
                Copyright © 2021 Zhao, Zhang, Ju, Li and Zheng.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 September 2020
                : 09 February 2021
                Page count
                Figures: 7, Tables: 4, Equations: 0, References: 44, Pages: 11, Words: 5197
                Funding
                Funded by: National Science Foundation for Young Scientists of China
                Award ID: 81802415
                Funded by: Shandong Provincial Natural Science Foundation 10.13039/501100007129
                Award ID: ZR2018PH025
                Categories
                Genetics
                Original Research

                Genetics
                gastric cancer,lncrna,mirna,mrna,cerna,prognosis
                Genetics
                gastric cancer, lncrna, mirna, mrna, cerna, prognosis

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