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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

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    Authors
    Memon, Danish
    Bi, J
    Miller, Crispin J
    Affiliation
    RNA Biology Group, CRUK Manchester Institute, The University of Manchester, Alderley Park, Manchester, SK10 4TG,
    Issue Date
    2019
    
    Metadata
    Show full item record
    Abstract
    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.
    Citation
    Memon D, Bi J, Miller CJ. In silico prediction of housekeeping long intergenic non-coding RNAs reveals HKlincR1 as an essential player in lung cancer cell survival. Sci Rep. 2019 May 14;9(1):7372.
    Journal
    Scientific Reports
    URI
    http://hdl.handle.net/10541/621915
    DOI
    10.1038/s41598-019-43758-7
    PubMed ID
    31089191
    Additional Links
    https://dx.doi.org/10.1038/s41598-019-43758-7
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41598-019-43758-7
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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