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Integrative analysis of ceRNA network reveals functional lncRNAs associated with independent recurrent prognosis in colon adenocarcinoma

BACKGROUND: Long non-coding RNAs (lncRNAs), acting as competing endogenous RNA (ceRNA) have been reported to regulate the expression of targeted genes by sponging miRNA in colon adenocarcinoma (COAD). METHODS: However, their potential implications for recurrence free survival prognosis and functiona...

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Autores principales: Mao, Yinling, Lv, Jiachen, Jiang, Li, Wang, Yihui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259330/
https://www.ncbi.nlm.nih.gov/pubmed/34225739
http://dx.doi.org/10.1186/s12935-021-02069-6
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author Mao, Yinling
Lv, Jiachen
Jiang, Li
Wang, Yihui
author_facet Mao, Yinling
Lv, Jiachen
Jiang, Li
Wang, Yihui
author_sort Mao, Yinling
collection PubMed
description BACKGROUND: Long non-coding RNAs (lncRNAs), acting as competing endogenous RNA (ceRNA) have been reported to regulate the expression of targeted genes by sponging miRNA in colon adenocarcinoma (COAD). METHODS: However, their potential implications for recurrence free survival prognosis and functional roles remains largely unclear in COAD. In this study, we downloaded the TCGA dataset (training dataset) and GSE39582 (validation dataset) of COAD patients with prognostic information. RESULTS: A total of 411 differentially expressed genes (DElncRNAs: 12 downregulated and 43 upregulated), 18 DE miRNAs (9 downregulated and 9 upregulated) and 338 DEmRNAs (113 downregulated and 225 upregulated) were identified in recurrence samples compared with non-recurrence samples with the thresholds of FDR < 0.05 and |log(2)FC|> 0.263. Based on six signature lncRNAs (LINC00899, LINC01503, PRKAG2-AS1, RAD21-AS1, SRRM2-AS1 and USP30-AS1), the risk score (RS) system was constructed. Two prognostic clinical features, including pathologic stage and RS model status were screened for building the nomogram survival model. Moreover, a recurrent-specific ceRNA network was successfully constructed with 2 signature lncRNAs, 4 miRNAs and 113 mRNAs. Furthermore, we further manifested that SRRM2-AS1 predicted a poor prognosis in COAD patients. Furthermore, knockdown of SRRM2-AS1 significantly suppressed cell proliferation, migration, invasion and EMT markers in HT-29 and SW1116 cells. CONCLUSION: These identified novel lncRNA signature and ceRNA network associated with recurrence prognosis might provide promising therapeutic targets for COAD patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02069-6.
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spelling pubmed-82593302021-07-06 Integrative analysis of ceRNA network reveals functional lncRNAs associated with independent recurrent prognosis in colon adenocarcinoma Mao, Yinling Lv, Jiachen Jiang, Li Wang, Yihui Cancer Cell Int Primary Research BACKGROUND: Long non-coding RNAs (lncRNAs), acting as competing endogenous RNA (ceRNA) have been reported to regulate the expression of targeted genes by sponging miRNA in colon adenocarcinoma (COAD). METHODS: However, their potential implications for recurrence free survival prognosis and functional roles remains largely unclear in COAD. In this study, we downloaded the TCGA dataset (training dataset) and GSE39582 (validation dataset) of COAD patients with prognostic information. RESULTS: A total of 411 differentially expressed genes (DElncRNAs: 12 downregulated and 43 upregulated), 18 DE miRNAs (9 downregulated and 9 upregulated) and 338 DEmRNAs (113 downregulated and 225 upregulated) were identified in recurrence samples compared with non-recurrence samples with the thresholds of FDR < 0.05 and |log(2)FC|> 0.263. Based on six signature lncRNAs (LINC00899, LINC01503, PRKAG2-AS1, RAD21-AS1, SRRM2-AS1 and USP30-AS1), the risk score (RS) system was constructed. Two prognostic clinical features, including pathologic stage and RS model status were screened for building the nomogram survival model. Moreover, a recurrent-specific ceRNA network was successfully constructed with 2 signature lncRNAs, 4 miRNAs and 113 mRNAs. Furthermore, we further manifested that SRRM2-AS1 predicted a poor prognosis in COAD patients. Furthermore, knockdown of SRRM2-AS1 significantly suppressed cell proliferation, migration, invasion and EMT markers in HT-29 and SW1116 cells. CONCLUSION: These identified novel lncRNA signature and ceRNA network associated with recurrence prognosis might provide promising therapeutic targets for COAD patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02069-6. BioMed Central 2021-07-05 /pmc/articles/PMC8259330/ /pubmed/34225739 http://dx.doi.org/10.1186/s12935-021-02069-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Mao, Yinling
Lv, Jiachen
Jiang, Li
Wang, Yihui
Integrative analysis of ceRNA network reveals functional lncRNAs associated with independent recurrent prognosis in colon adenocarcinoma
title Integrative analysis of ceRNA network reveals functional lncRNAs associated with independent recurrent prognosis in colon adenocarcinoma
title_full Integrative analysis of ceRNA network reveals functional lncRNAs associated with independent recurrent prognosis in colon adenocarcinoma
title_fullStr Integrative analysis of ceRNA network reveals functional lncRNAs associated with independent recurrent prognosis in colon adenocarcinoma
title_full_unstemmed Integrative analysis of ceRNA network reveals functional lncRNAs associated with independent recurrent prognosis in colon adenocarcinoma
title_short Integrative analysis of ceRNA network reveals functional lncRNAs associated with independent recurrent prognosis in colon adenocarcinoma
title_sort integrative analysis of cerna network reveals functional lncrnas associated with independent recurrent prognosis in colon adenocarcinoma
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259330/
https://www.ncbi.nlm.nih.gov/pubmed/34225739
http://dx.doi.org/10.1186/s12935-021-02069-6
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