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LncRNA Hmrhl regulates expression of cancer related genes in chronic myelogenous leukemia through chromatin association

Long non-coding RNA has emerged as a key regulator of myriad gene functions. One such lncRNA mrhl, reported by our group, was found to have important role in spermatogenesis and embryonic development in mouse. Recently, its human homolog, Hmrhl was shown to have differential expression in several ty...

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Autores principales: Choudhury, Subhendu Roy, Dutta, Sangeeta, Bhaduri, Utsa, Rao, Manchanahalli R Satyanarayana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559160/
https://www.ncbi.nlm.nih.gov/pubmed/34734184
http://dx.doi.org/10.1093/narcan/zcab042
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author Choudhury, Subhendu Roy
Dutta, Sangeeta
Bhaduri, Utsa
Rao, Manchanahalli R Satyanarayana
author_facet Choudhury, Subhendu Roy
Dutta, Sangeeta
Bhaduri, Utsa
Rao, Manchanahalli R Satyanarayana
author_sort Choudhury, Subhendu Roy
collection PubMed
description Long non-coding RNA has emerged as a key regulator of myriad gene functions. One such lncRNA mrhl, reported by our group, was found to have important role in spermatogenesis and embryonic development in mouse. Recently, its human homolog, Hmrhl was shown to have differential expression in several type of cancers. In the present study, we further characterize molecular features of Hmrhl and gain insight into its functional role in leukemia by gene silencing and transcriptome-based studies. Results indicate its high expression in CML patient samples as well as in K562 cell line. Silencing experiments suggest role of Hmrhl in cell proliferation, migration & invasion. RNA-seq and ChiRP-seq data analysis further revealed its association with important biological processes, including perturbed expression of crucial TFs and cancer-related genes. Among them ZIC1, PDGRFβ and TP53 were identified as regulatory targets, with high possibility of triplex formation by Hmrhl at their promoter site. Further, overexpression of PDGRFβ in Hmrhl silenced cells resulted in rescue effect of cancer associated cellular phenotypes. In addition, we also found TAL-1 to be a potential regulator of Hmrhl expression in K562 cells. Thus, we hypothesize that Hmrhl lncRNA may play a significant role in the pathobiology of CML.
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spelling pubmed-85591602021-11-02 LncRNA Hmrhl regulates expression of cancer related genes in chronic myelogenous leukemia through chromatin association Choudhury, Subhendu Roy Dutta, Sangeeta Bhaduri, Utsa Rao, Manchanahalli R Satyanarayana NAR Cancer Cancer Gene Regulation, Chromatin, and Epigenetics Long non-coding RNA has emerged as a key regulator of myriad gene functions. One such lncRNA mrhl, reported by our group, was found to have important role in spermatogenesis and embryonic development in mouse. Recently, its human homolog, Hmrhl was shown to have differential expression in several type of cancers. In the present study, we further characterize molecular features of Hmrhl and gain insight into its functional role in leukemia by gene silencing and transcriptome-based studies. Results indicate its high expression in CML patient samples as well as in K562 cell line. Silencing experiments suggest role of Hmrhl in cell proliferation, migration & invasion. RNA-seq and ChiRP-seq data analysis further revealed its association with important biological processes, including perturbed expression of crucial TFs and cancer-related genes. Among them ZIC1, PDGRFβ and TP53 were identified as regulatory targets, with high possibility of triplex formation by Hmrhl at their promoter site. Further, overexpression of PDGRFβ in Hmrhl silenced cells resulted in rescue effect of cancer associated cellular phenotypes. In addition, we also found TAL-1 to be a potential regulator of Hmrhl expression in K562 cells. Thus, we hypothesize that Hmrhl lncRNA may play a significant role in the pathobiology of CML. Oxford University Press 2021-11-01 /pmc/articles/PMC8559160/ /pubmed/34734184 http://dx.doi.org/10.1093/narcan/zcab042 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of NAR Cancer. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Cancer Gene Regulation, Chromatin, and Epigenetics
Choudhury, Subhendu Roy
Dutta, Sangeeta
Bhaduri, Utsa
Rao, Manchanahalli R Satyanarayana
LncRNA Hmrhl regulates expression of cancer related genes in chronic myelogenous leukemia through chromatin association
title LncRNA Hmrhl regulates expression of cancer related genes in chronic myelogenous leukemia through chromatin association
title_full LncRNA Hmrhl regulates expression of cancer related genes in chronic myelogenous leukemia through chromatin association
title_fullStr LncRNA Hmrhl regulates expression of cancer related genes in chronic myelogenous leukemia through chromatin association
title_full_unstemmed LncRNA Hmrhl regulates expression of cancer related genes in chronic myelogenous leukemia through chromatin association
title_short LncRNA Hmrhl regulates expression of cancer related genes in chronic myelogenous leukemia through chromatin association
title_sort lncrna hmrhl regulates expression of cancer related genes in chronic myelogenous leukemia through chromatin association
topic Cancer Gene Regulation, Chromatin, and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559160/
https://www.ncbi.nlm.nih.gov/pubmed/34734184
http://dx.doi.org/10.1093/narcan/zcab042
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