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Background <p>Long intergenic non-coding RNAs (lincRNAs) and single nucleotide polymorphisms (SNPs) have been associated with cancers for years, yet the molecular mechanism is mostly unclear. The secondary structure of lincRNAs is often crucial for their biological function but can be disrupted by SNPs. However, only a small number of studies investigated how lincRNAs function through secondary structure. Given that the vast majority of cancer-related SNPs are located mainly in non-coding regions, there is a large potential for associating SNPs to disrupted structure in lincRNAs.</p> Methods <p>To estimate the structural impacts of cancer-associated SNPs on lincRNAs, we predicted local secondary structures for lincRNAs and computed structural distances between structural ensembles of the wild-type and mutant sequences. Manual literature curation was performed to study the function of lincRNAs that are structurally disrupted by cancer-associated SNPs. By integrating with RBP binding sites annotation, we estimated the impacts of structural changes from cancer-associated SNPs on the protein binding of lincRNAs.</p> Results <p>We predict 559 SNPs to cause significant structural disruption in 231 lincRNAs using RNAsnp (<i>P</i>-value &lt; 0.1). In addition, we find that these disrupted regions have the potential to alter the binding ability of lincRNAs with RBPs. An example is the structural change in the lincRNA small nucleolar RNA host gene 25 (SNHG25), which overlaps the binding site of protein insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) in glioblastoma multiforme.</p> Conclusions <p>The results show the importance of the lincRNA secondary structure in understanding their biological function, especially the structural changes from SNPs in cancer. The predicted structural change in lincRNA SNHG25 holds a potential insight into the mechanism of protein IGF2BP2 in recognizing RNA methylation signals in glioblastoma multiforme.</p>

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Associating cancer-related RNA structure disrupting SNPs in LincRNAs to function

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月12日

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  • Xueer Han,
  • Christian Anthon,
  • Adrian Sven Geissler,
  • Radhakrishnan Sabarinathan,
  • Stefan Ernst Seemann,
  • Jakob Hull Havgaard,
  • Jan Gorodkin

摘要

Background

Long intergenic non-coding RNAs (lincRNAs) and single nucleotide polymorphisms (SNPs) have been associated with cancers for years, yet the molecular mechanism is mostly unclear. The secondary structure of lincRNAs is often crucial for their biological function but can be disrupted by SNPs. However, only a small number of studies investigated how lincRNAs function through secondary structure. Given that the vast majority of cancer-related SNPs are located mainly in non-coding regions, there is a large potential for associating SNPs to disrupted structure in lincRNAs.

Methods

To estimate the structural impacts of cancer-associated SNPs on lincRNAs, we predicted local secondary structures for lincRNAs and computed structural distances between structural ensembles of the wild-type and mutant sequences. Manual literature curation was performed to study the function of lincRNAs that are structurally disrupted by cancer-associated SNPs. By integrating with RBP binding sites annotation, we estimated the impacts of structural changes from cancer-associated SNPs on the protein binding of lincRNAs.

Results

We predict 559 SNPs to cause significant structural disruption in 231 lincRNAs using RNAsnp (P-value < 0.1). In addition, we find that these disrupted regions have the potential to alter the binding ability of lincRNAs with RBPs. An example is the structural change in the lincRNA small nucleolar RNA host gene 25 (SNHG25), which overlaps the binding site of protein insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) in glioblastoma multiforme.

Conclusions

The results show the importance of the lincRNA secondary structure in understanding their biological function, especially the structural changes from SNPs in cancer. The predicted structural change in lincRNA SNHG25 holds a potential insight into the mechanism of protein IGF2BP2 in recognizing RNA methylation signals in glioblastoma multiforme.