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In silico prediction of housekeeping long intergenic non-coding RNAs reveals HKlincR1 as an essential player in lung cancer cell survival
Prioritising long intergenic noncoding RNAs (lincRNAs) for functional characterisation is a significant challenge. Here we applied computational approaches to discover lincRNAs expected to play a critical housekeeping (HK) role within the cell. Using the Illumina Human BodyMap RNA sequencing dataset...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517443/ https://www.ncbi.nlm.nih.gov/pubmed/31089191 http://dx.doi.org/10.1038/s41598-019-43758-7 |
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author | Memon, Danish Bi, Jing Miller, Crispin J. |
author_facet | Memon, Danish Bi, Jing Miller, Crispin J. |
author_sort | Memon, Danish |
collection | PubMed |
description | Prioritising long intergenic noncoding RNAs (lincRNAs) for functional characterisation is a significant challenge. Here we applied computational approaches to discover lincRNAs expected to play a critical housekeeping (HK) role within the cell. Using the Illumina Human BodyMap RNA sequencing dataset as a starting point, we first identified lincRNAs ubiquitously expressed across a panel of human tissues. This list was then further refined by reference to conservation score, secondary structure and promoter DNA methylation status. Finally, we used tumour expression and copy number data to identify lincRNAs rarely downregulated or deleted in multiple tumour types. The resulting list of candidate essential lincRNAs was then subjected to co-expression analyses using independent data from ENCODE and The Cancer Genome Atlas (TCGA). This identified a substantial subset with a predicted role in DNA replication and cell cycle regulation. One of these, HKlincR1, was selected for further characterisation. Depletion of HKlincR1 affected cell growth in multiple lung cancer cell lines, and led to disruption of genes involved in cell growth and viability. In addition, HKlincR1 expression was correlated with overall survival in lung adenocarcinoma patients. Our in silico studies therefore reveal a set of housekeeping noncoding RNAs of interest both in terms of their role in normal homeostasis, and their relevance in tumour growth and maintenance. |
format | Online Article Text |
id | pubmed-6517443 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65174432019-05-24 In silico prediction of housekeeping long intergenic non-coding RNAs reveals HKlincR1 as an essential player in lung cancer cell survival Memon, Danish Bi, Jing Miller, Crispin J. Sci Rep Article Prioritising long intergenic noncoding RNAs (lincRNAs) for functional characterisation is a significant challenge. Here we applied computational approaches to discover lincRNAs expected to play a critical housekeeping (HK) role within the cell. Using the Illumina Human BodyMap RNA sequencing dataset as a starting point, we first identified lincRNAs ubiquitously expressed across a panel of human tissues. This list was then further refined by reference to conservation score, secondary structure and promoter DNA methylation status. Finally, we used tumour expression and copy number data to identify lincRNAs rarely downregulated or deleted in multiple tumour types. The resulting list of candidate essential lincRNAs was then subjected to co-expression analyses using independent data from ENCODE and The Cancer Genome Atlas (TCGA). This identified a substantial subset with a predicted role in DNA replication and cell cycle regulation. One of these, HKlincR1, was selected for further characterisation. Depletion of HKlincR1 affected cell growth in multiple lung cancer cell lines, and led to disruption of genes involved in cell growth and viability. In addition, HKlincR1 expression was correlated with overall survival in lung adenocarcinoma patients. Our in silico studies therefore reveal a set of housekeeping noncoding RNAs of interest both in terms of their role in normal homeostasis, and their relevance in tumour growth and maintenance. Nature Publishing Group UK 2019-05-14 /pmc/articles/PMC6517443/ /pubmed/31089191 http://dx.doi.org/10.1038/s41598-019-43758-7 Text en © The Author(s) 2019 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Memon, Danish Bi, Jing Miller, Crispin J. In silico prediction of housekeeping long intergenic non-coding RNAs reveals HKlincR1 as an essential player in lung cancer cell survival |
title | In silico prediction of housekeeping long intergenic non-coding RNAs reveals HKlincR1 as an essential player in lung cancer cell survival |
title_full | In silico prediction of housekeeping long intergenic non-coding RNAs reveals HKlincR1 as an essential player in lung cancer cell survival |
title_fullStr | In silico prediction of housekeeping long intergenic non-coding RNAs reveals HKlincR1 as an essential player in lung cancer cell survival |
title_full_unstemmed | In silico prediction of housekeeping long intergenic non-coding RNAs reveals HKlincR1 as an essential player in lung cancer cell survival |
title_short | In silico prediction of housekeeping long intergenic non-coding RNAs reveals HKlincR1 as an essential player in lung cancer cell survival |
title_sort | in silico prediction of housekeeping long intergenic non-coding rnas reveals hklincr1 as an essential player in lung cancer cell survival |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517443/ https://www.ncbi.nlm.nih.gov/pubmed/31089191 http://dx.doi.org/10.1038/s41598-019-43758-7 |
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