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A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma

The HAND2-AS1 (HAND2 Antisense RNA 1) Long noncoding RNA (lncRNA) has emerged as a participant in the initiation of various cancer types, underscoring its pivotal involvement in both oncological processes and immune responses. To gain deeper insights into the functional nuances of HAND2-AS1 and iden...

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Autores principales: Samadi, Pouria, Shahnazari, Mina, Shekari, Abolfazl, Maghool, Fatemeh, Jalali, Akram
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693120/
https://www.ncbi.nlm.nih.gov/pubmed/38042769
http://dx.doi.org/10.1186/s12935-023-03163-7
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author Samadi, Pouria
Shahnazari, Mina
Shekari, Abolfazl
Maghool, Fatemeh
Jalali, Akram
author_facet Samadi, Pouria
Shahnazari, Mina
Shekari, Abolfazl
Maghool, Fatemeh
Jalali, Akram
author_sort Samadi, Pouria
collection PubMed
description The HAND2-AS1 (HAND2 Antisense RNA 1) Long noncoding RNA (lncRNA) has emerged as a participant in the initiation of various cancer types, underscoring its pivotal involvement in both oncological processes and immune responses. To gain deeper insights into the functional nuances of HAND2-AS1 and identify novel avenues for cancer immunotherapy, a comprehensive evaluation of this gene was undertaken. Here, based on the co-expression network analysis and construction of interacting lncRNA–mRNA genes, we introduce the HAND2-AS1 lncRNA, emphasizing its key roles in tumorigenesis and immune regulation. Our study spans across 33 distinct cancer types, revealing the HAND2-AS1’s aberrant expression patterns, methylation variations, mutational signatures, and immune engagement. Across a majority of tumors, HAND2-AS1 exhibited a propensity for down-regulation, remarkably an association with poor survival outcomes. The outcomes of functional enrichment analyses strongly suggest HAND2-AS1’s engagement in tumor progression and its association with various immune pathways across diverse tumor classifications. Additionally, a positive correlation emerged between HAND2-AS1 expression and the infiltration levels of key immune cells, encompassing not only immunosuppressive entities such as tumor-associated macrophages, cancer-associated fibroblasts, and Tregs, but also immune effector cells like NK cells and CD8+ T cells, spanning a pan-cancer context. Furthermore, the differential expression of HAND2-AS1 appears to have downstream consequences on various pathways, thus implicating it as a potential regulator in diverse cancer types. Finally, we have employed CRC tumor and normal samples to carry out clinical validation of HAND2-AS1. Our study unveils HAND2-AS1’s potential as a pan-cancer tumor suppressor, and its essential role in the tumorigenesis and immune surveillance. The increased HAND2-AS1 expression emerges as a promising candidate for prognostic evaluation, therapeutic strategy, and a focal point for immunotherapeutic interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-03163-7.
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spelling pubmed-106931202023-12-03 A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma Samadi, Pouria Shahnazari, Mina Shekari, Abolfazl Maghool, Fatemeh Jalali, Akram Cancer Cell Int Research The HAND2-AS1 (HAND2 Antisense RNA 1) Long noncoding RNA (lncRNA) has emerged as a participant in the initiation of various cancer types, underscoring its pivotal involvement in both oncological processes and immune responses. To gain deeper insights into the functional nuances of HAND2-AS1 and identify novel avenues for cancer immunotherapy, a comprehensive evaluation of this gene was undertaken. Here, based on the co-expression network analysis and construction of interacting lncRNA–mRNA genes, we introduce the HAND2-AS1 lncRNA, emphasizing its key roles in tumorigenesis and immune regulation. Our study spans across 33 distinct cancer types, revealing the HAND2-AS1’s aberrant expression patterns, methylation variations, mutational signatures, and immune engagement. Across a majority of tumors, HAND2-AS1 exhibited a propensity for down-regulation, remarkably an association with poor survival outcomes. The outcomes of functional enrichment analyses strongly suggest HAND2-AS1’s engagement in tumor progression and its association with various immune pathways across diverse tumor classifications. Additionally, a positive correlation emerged between HAND2-AS1 expression and the infiltration levels of key immune cells, encompassing not only immunosuppressive entities such as tumor-associated macrophages, cancer-associated fibroblasts, and Tregs, but also immune effector cells like NK cells and CD8+ T cells, spanning a pan-cancer context. Furthermore, the differential expression of HAND2-AS1 appears to have downstream consequences on various pathways, thus implicating it as a potential regulator in diverse cancer types. Finally, we have employed CRC tumor and normal samples to carry out clinical validation of HAND2-AS1. Our study unveils HAND2-AS1’s potential as a pan-cancer tumor suppressor, and its essential role in the tumorigenesis and immune surveillance. The increased HAND2-AS1 expression emerges as a promising candidate for prognostic evaluation, therapeutic strategy, and a focal point for immunotherapeutic interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-023-03163-7. BioMed Central 2023-12-02 /pmc/articles/PMC10693120/ /pubmed/38042769 http://dx.doi.org/10.1186/s12935-023-03163-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/ Open Access This 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
Samadi, Pouria
Shahnazari, Mina
Shekari, Abolfazl
Maghool, Fatemeh
Jalali, Akram
A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma
title A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma
title_full A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma
title_fullStr A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma
title_full_unstemmed A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma
title_short A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma
title_sort pan-cancer analysis indicates long noncoding rna hand2-as1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693120/
https://www.ncbi.nlm.nih.gov/pubmed/38042769
http://dx.doi.org/10.1186/s12935-023-03163-7
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