Journal
NPJ GENOMIC MEDICINE
Volume 7, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41525-022-00305-0
Keywords
-
Categories
Funding
- National Key R&D Program of China [2021YFC2501000]
- National Natural Science Foundation of China [82030089]
- CAMS Innovation Fund for Medical Sciences [2021-1-I2M-018]
- Sanming Project of Medicine in Shenzhen [SZSM201812062]
Ask authors/readers for more resources
This study revealed the prevalence and clinical relevance of 3'-UTR somatic mutations in tumorigenesis. In addition to affecting miRNAs, these mutations also perturb RBPs binding, APA, and m6A RNA modification. The study also identified several cancer-related genes that facilitate tumorigenesis at the protein and posttranscriptional regulation levels.
The 3 ' untranslated region (3 '-UTR) is the vital element regulating gene expression, but most studies have focused on variations in RNA-binding proteins (RBPs), miRNAs, alternative polyadenylation (APA) and RNA modifications. To explore the posttranscriptional function of 3 '-UTR somatic mutations in tumorigenesis, we collected whole-genome data from 2413 patients across 18 cancer types. Our updated algorithm, PIVar, revealed 25,216 3 '-UTR posttranscriptional impairment-related SNVs (3 '-UTR piSNVs) spanning 2930 genes; 24 related RBPs were significantly enriched. The somatic 3 '-UTR piSNV ratio was markedly increased across all 18 cancer types, which was associated with worse survival for four cancer types. Several cancer-related genes appeared to facilitate tumorigenesis at the protein and posttranscriptional regulation levels, whereas some 3 '-UTR piSNV-affected genes functioned mainly via posttranscriptional mechanisms. Moreover, we assessed immune cell and checkpoint characteristics between the high/low 3 '-UTR piSNV ratio groups and predicted 80 compounds associated with the 3 '-UTR piSNV-affected gene expression signature. In summary, our study revealed the prevalence and clinical relevance of 3 '-UTR piSNVs in cancers, and also demonstrates that in addition to affecting miRNAs, 3 '-UTR piSNVs perturb RBPs binding, APA and m6A RNA modification, which emphasized the importance of considering 3 '-UTR piSNVs in cancer biology.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available