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Identification of novel key regulatory lncRNAs in gastric adenocarcinoma

BACKGROUND: Stomach adenocarcinoma (STAD) is one of the most common and deadly cancers worldwide. Recent evidence has demonstrated that dysregulation of long noncoding RNAs (lncRNA) is associated with different hallmarks of cancer. lncRNAs also were suggested as novel promising biomarkers for cancer...

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Autores principales: Razavi, Houri, Katanforosh, Ali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9080188/
https://www.ncbi.nlm.nih.gov/pubmed/35525925
http://dx.doi.org/10.1186/s12864-022-08578-6
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author Razavi, Houri
Katanforosh, Ali
author_facet Razavi, Houri
Katanforosh, Ali
author_sort Razavi, Houri
collection PubMed
description BACKGROUND: Stomach adenocarcinoma (STAD) is one of the most common and deadly cancers worldwide. Recent evidence has demonstrated that dysregulation of long noncoding RNAs (lncRNA) is associated with different hallmarks of cancer. lncRNAs also were suggested as novel promising biomarkers for cancer diagnosis and prognosis. Despite these previous investigations, the expression pattern, diagnostic role, and hallmark association of lncRNAs in STAD remain unclear. RESULTS: In this study, The STAD lncRNA-mRNA network was constructed based on RNAs that differentially expressed among tumor and normal samples and had a strong expression correlation with others. The high degree nodes of the network were associated with overall survival. In addition, we found that the hubs’ regulatory roles have previously been confirmed in different types of cancers by literature. For example, the HCG22 hub inhibited cell proliferation and invasion and induced apoptosis in oral squamous cell carcinoma (OSCC) cells. The levels of PCNA, Vimentin, and Bcl2 were decreased and E-cadherin and Bax expression was elevated in OSCC cells after HCG22 overexpression. Additionally, HCG22 overexpression inhibited the Akt, mTOR, and Wnt/β-catenin pathways. Then lncRNAs were mapped to their related GO terms and cancer hallmarks. Based on these mappings, we predict the hallmarks that might be associated with each lncRNA. Finally, the literature review confirmed our prediction. Among the 20 lncRNAs of the STAD network, 11 lncRNAs (LINC02560, SOX21-AS1, C5orf66-AS1, HCG22, PGM5-AS1, NALT1, ENSG00000241224.2, TINCR, MIR205HG, HNF4A-AS1, ENSG00000262756) demonstrated expression correlation with overall survival (OS). Based on expression analysis, survival analysis, hallmark associations, and literature review, LINC02560, SOX21-AS1, C5orf66-AS1, HCG22, PGM5-AS1, NALT1, ENSG00000241224.2, TINCR, MIR205HG, HNF4A-AS1 plays a regulatory role in STAD. For example, our prediction of association between C5orf66-AS1 expression dysregulation and “sustaining proliferative signal” and “Activating invasion and metastasis” has been confirmed in STAD, OSCC and cervical cancer. Finally, we developed a lncRNA signature with SOX21-AS1 and LINC02560, which classified patients into high and low-risk subgroups with significantly different survival outcomes. The mortality rate of the high-risk patients was significantly higher compared to the low-risk patients (28/1% vs 60.13). CONCLUSION: These findings help in designing more precise and detailed experimental studies to find STAD biomarkers and therapeutic targets. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-022-08578-6.
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spelling pubmed-90801882022-05-09 Identification of novel key regulatory lncRNAs in gastric adenocarcinoma Razavi, Houri Katanforosh, Ali BMC Genomics Research BACKGROUND: Stomach adenocarcinoma (STAD) is one of the most common and deadly cancers worldwide. Recent evidence has demonstrated that dysregulation of long noncoding RNAs (lncRNA) is associated with different hallmarks of cancer. lncRNAs also were suggested as novel promising biomarkers for cancer diagnosis and prognosis. Despite these previous investigations, the expression pattern, diagnostic role, and hallmark association of lncRNAs in STAD remain unclear. RESULTS: In this study, The STAD lncRNA-mRNA network was constructed based on RNAs that differentially expressed among tumor and normal samples and had a strong expression correlation with others. The high degree nodes of the network were associated with overall survival. In addition, we found that the hubs’ regulatory roles have previously been confirmed in different types of cancers by literature. For example, the HCG22 hub inhibited cell proliferation and invasion and induced apoptosis in oral squamous cell carcinoma (OSCC) cells. The levels of PCNA, Vimentin, and Bcl2 were decreased and E-cadherin and Bax expression was elevated in OSCC cells after HCG22 overexpression. Additionally, HCG22 overexpression inhibited the Akt, mTOR, and Wnt/β-catenin pathways. Then lncRNAs were mapped to their related GO terms and cancer hallmarks. Based on these mappings, we predict the hallmarks that might be associated with each lncRNA. Finally, the literature review confirmed our prediction. Among the 20 lncRNAs of the STAD network, 11 lncRNAs (LINC02560, SOX21-AS1, C5orf66-AS1, HCG22, PGM5-AS1, NALT1, ENSG00000241224.2, TINCR, MIR205HG, HNF4A-AS1, ENSG00000262756) demonstrated expression correlation with overall survival (OS). Based on expression analysis, survival analysis, hallmark associations, and literature review, LINC02560, SOX21-AS1, C5orf66-AS1, HCG22, PGM5-AS1, NALT1, ENSG00000241224.2, TINCR, MIR205HG, HNF4A-AS1 plays a regulatory role in STAD. For example, our prediction of association between C5orf66-AS1 expression dysregulation and “sustaining proliferative signal” and “Activating invasion and metastasis” has been confirmed in STAD, OSCC and cervical cancer. Finally, we developed a lncRNA signature with SOX21-AS1 and LINC02560, which classified patients into high and low-risk subgroups with significantly different survival outcomes. The mortality rate of the high-risk patients was significantly higher compared to the low-risk patients (28/1% vs 60.13). CONCLUSION: These findings help in designing more precise and detailed experimental studies to find STAD biomarkers and therapeutic targets. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-022-08578-6. BioMed Central 2022-05-07 /pmc/articles/PMC9080188/ /pubmed/35525925 http://dx.doi.org/10.1186/s12864-022-08578-6 Text en © The Author(s) 2022 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 Research
Razavi, Houri
Katanforosh, Ali
Identification of novel key regulatory lncRNAs in gastric adenocarcinoma
title Identification of novel key regulatory lncRNAs in gastric adenocarcinoma
title_full Identification of novel key regulatory lncRNAs in gastric adenocarcinoma
title_fullStr Identification of novel key regulatory lncRNAs in gastric adenocarcinoma
title_full_unstemmed Identification of novel key regulatory lncRNAs in gastric adenocarcinoma
title_short Identification of novel key regulatory lncRNAs in gastric adenocarcinoma
title_sort identification of novel key regulatory lncrnas in gastric adenocarcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9080188/
https://www.ncbi.nlm.nih.gov/pubmed/35525925
http://dx.doi.org/10.1186/s12864-022-08578-6
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