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Pan-cancer analysis of transcripts encoding novel open-reading frames (nORFs) and their potential biological
Chaitanya Erady1, Adam Boxall1, Shraddha Puntambekar2
1Department of Genetics, University of Cambridge, Downing Site, Cambridge, CB2 3EH, UK.
NPJ Genomic Medicine
|January 26, 2021
Summary
Novel open reading frames (nORFs) are frequently dysregulated in cancer, with some showing prognostic value and potential as therapeutic targets. This study systematically identifies and characterizes nORFs across 22 cancer types.
Area of Science:
- Genomics
- Cancer Biology
- Bioinformatics
Background:
- Uncharacterized open reading frames, termed novel open reading frames (nORFs), may represent untapped sources for novel therapeutics.
- Systematic identification and characterization of nORFs and their products in cancer are lacking.
Purpose of the Study:
- To systematically identify and characterize transcripts encoding nORFs and their translation products in cancer.
- To investigate the dysregulation and potential prognostic value of nORFs in various cancer types.
- To explore the therapeutic potential of targeting nORF-encoded proteins.
Main Methods:
- Utilized a curated nORFs database (nORFs.org).
- Analyzed RNA-Seq data from The Cancer Genome Atlas (TCGA) and Genotype-Expression (GTEx) consortiums across 22 cancer types.
- Performed in silico screening for inhibitors against specific nORF-encoded proteins.
Main Results:
- Identified frequent expression of nORFs in cancer and matched normal tissues.
- Demonstrated extensive transcript-level dysregulation of nORFs in cancer.
- Showed a subset of nORFs associated with patient survival, indicating prognostic potential.
- Confirmed nORF products can form protein-like structures with post-translational modifications.
- Identified potential therapeutic targets for nORF-encoded proteins disrupted in stomach and esophageal cancer.
Conclusions:
- nORFs are significantly dysregulated in cancer and hold potential as prognostic biomarkers.
- nORF-encoded proteins represent a novel class of potential therapeutic targets.
- This study provides a foundation for future research into nORF functions and therapeutic applications in oncology.
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