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Published on: May 30, 2025
A Catalogue of Putative cis-Regulatory Interactions Between Long Non-coding RNAs and Proximal Coding Genes Based on
1Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden swaraj.basu@gu.se erik.larsson@gu.se.
Abstract:
Antisense transcripts and other long non-coding RNAs are pervasive in mammalian cells, and some of these molecules have been proposed to regulate proximal protein-coding genes in cis For example, non-coding transcription can contribute to inactivation of tumor suppressor genes in cancer, and antisense transcripts have been implicated in the epigenetic inactivation of imprinted genes. However, our knowledge is still limited and more such regulatory interactions likely await discovery. Here, we make use of available gene expression data from a large compendium of human tumors to generate hypotheses regarding non-coding-to-coding cis-regulatory relationships with emphasis on negative associations, as these are less likely to arise for reasons other than cis-regulation. We document a large number of possible regulatory interactions, including 193 coding/non-coding pairs that show expression patterns compatible with negative cis-regulation. Importantly, by this approach we capture several known cases, and many of the involved coding genes have known roles in cancer. Our study provides a large catalog of putative non-coding/coding cis-regulatory pairs that may serve as a basis for further experimental validation and characterization.
Insights
Researchers identified 193 potential negative cis-regulatory pairs between non-coding RNAs and protein-coding genes using human tumor data. This catalog aids in understanding gene regulation and cancer mechanisms.
Area of Science:
- Genomics
- Molecular Biology
- Cancer Research
Background:
- Long non-coding RNAs (lncRNAs) and antisense transcripts are common in mammalian cells.
- Some lncRNAs may regulate nearby protein-coding genes in cis.
- Known roles include tumor suppressor gene inactivation and epigenetic gene silencing.
Purpose of the Study:
- To identify novel non-coding RNA to protein-coding gene cis-regulatory relationships.
- To focus on negative regulatory associations, which are less likely to be coincidental.
- To leverage large-scale human tumor gene expression data for hypothesis generation.
Main Methods:
- Analysis of a large compendium of human tumor gene expression data.
- Generation of hypotheses for non-coding to coding cis-regulatory interactions.
- Prioritization of negative expression associations as indicators of cis-regulation.
Main Results:
- A significant number of potential cis-regulatory interactions were identified.
- 193 coding/non-coding pairs exhibited expression patterns consistent with negative cis-regulation.
- Known regulatory interactions were successfully captured, validating the approach.
Conclusions:
- The study provides a substantial catalog of putative non-coding/coding cis-regulatory pairs.
- These findings offer a foundation for experimental validation of novel gene regulation mechanisms.
- The identified pairs may have implications for understanding cancer biology.
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