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A hybrid approach to assess the structural impact of long noncoding RNA mutations uncovers key NEAT1 interactions in colorectal cancer

Aydın, Efe LU ; Saus, Ester ; Chorostecki, Uciel and Gabaldón, Toni (2023) In IUBMB Life 75(7). p.566-579
Abstract

Long noncoding RNAs (lncRNAs) are emerging players in cancer and they entail potential as prognostic biomarkers or therapeutic targets. Earlier studies have identified somatic mutations in lncRNAs that are associated with tumor relapse after therapy, but the underlying mechanisms behind these associations remain unknown. Given the relevance of secondary structure for the function of some lncRNAs, some of these mutations may have a functional impact through structural disturbance. Here, we examined the potential structural and functional impact of a novel A > G point mutation in NEAT1 that has been recurrently observed in tumors of colorectal cancer patients experiencing relapse after treatment. Here, we used the nextPARS structural... (More)

Long noncoding RNAs (lncRNAs) are emerging players in cancer and they entail potential as prognostic biomarkers or therapeutic targets. Earlier studies have identified somatic mutations in lncRNAs that are associated with tumor relapse after therapy, but the underlying mechanisms behind these associations remain unknown. Given the relevance of secondary structure for the function of some lncRNAs, some of these mutations may have a functional impact through structural disturbance. Here, we examined the potential structural and functional impact of a novel A > G point mutation in NEAT1 that has been recurrently observed in tumors of colorectal cancer patients experiencing relapse after treatment. Here, we used the nextPARS structural probing approach to provide first empirical evidence that this mutation alters NEAT1 structure. We further evaluated the potential effects of this structural alteration using computational tools and found that this mutation likely alters the binding propensities of several NEAT1-interacting miRNAs. Differential expression analysis on these miRNA networks shows upregulation of Vimentin, consistent with previous findings. We propose a hybrid pipeline that can be used to explore the potential functional effects of lncRNA somatic mutations.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
IUBMB Life
volume
75
issue
7
pages
566 - 579
publisher
Wiley-Blackwell
external identifiers
  • scopus:85150996572
  • pmid:36971476
ISSN
1521-6543
DOI
10.1002/iub.2710
language
English
LU publication?
yes
id
cdf93e5c-656f-4703-ba01-e865faaa51bb
date added to LUP
2023-05-24 14:10:03
date last changed
2024-09-21 12:29:15
@article{cdf93e5c-656f-4703-ba01-e865faaa51bb,
  abstract     = {{<p>Long noncoding RNAs (lncRNAs) are emerging players in cancer and they entail potential as prognostic biomarkers or therapeutic targets. Earlier studies have identified somatic mutations in lncRNAs that are associated with tumor relapse after therapy, but the underlying mechanisms behind these associations remain unknown. Given the relevance of secondary structure for the function of some lncRNAs, some of these mutations may have a functional impact through structural disturbance. Here, we examined the potential structural and functional impact of a novel A &gt; G point mutation in NEAT1 that has been recurrently observed in tumors of colorectal cancer patients experiencing relapse after treatment. Here, we used the nextPARS structural probing approach to provide first empirical evidence that this mutation alters NEAT1 structure. We further evaluated the potential effects of this structural alteration using computational tools and found that this mutation likely alters the binding propensities of several NEAT1-interacting miRNAs. Differential expression analysis on these miRNA networks shows upregulation of Vimentin, consistent with previous findings. We propose a hybrid pipeline that can be used to explore the potential functional effects of lncRNA somatic mutations.</p>}},
  author       = {{Aydın, Efe and Saus, Ester and Chorostecki, Uciel and Gabaldón, Toni}},
  issn         = {{1521-6543}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{566--579}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{IUBMB Life}},
  title        = {{A hybrid approach to assess the structural impact of long noncoding RNA mutations uncovers key NEAT1 interactions in colorectal cancer}},
  url          = {{http://dx.doi.org/10.1002/iub.2710}},
  doi          = {{10.1002/iub.2710}},
  volume       = {{75}},
  year         = {{2023}},
}