Large-Scale Alternative Polyadenylation-Wide Association Studies to Identify Putative Cancer Susceptibility Genes

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F24%3A00587732" target="_blank" >RIV/68378041:_____/24:00587732 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/24:10482925 RIV/00216208:11140/24:10482925

Result on the web

<a href="https://aacrjournals.org/cancerres/article-abstract/84/16/2707/746872/Large-Scale-Alternative-Polyadenylation-Wide?redirectedFrom=fulltext" target="_blank" >https://aacrjournals.org/cancerres/article-abstract/84/16/2707/746872/Large-Scale-Alternative-Polyadenylation-Wide?redirectedFrom=fulltext</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1158/0008-5472.CAN-24-0521" target="_blank" >10.1158/0008-5472.CAN-24-0521</a>

Result language

angličtina

Original language name

Large-Scale Alternative Polyadenylation-Wide Association Studies to Identify Putative Cancer Susceptibility Genes

Original language description

Alternative polyadenylation (APA) modulates mRNA processing in the 3′-untranslated regions (3′ UTR), affecting mRNA stability and translation efficiency. Research into genetically regulated APA has the potential to provide insights into cancer risk. In this study, we conducted large APA-wide association studies to investigate associations between APA levels and cancer risk. Genetic models were built to predict APA levels in multiple tissues using genotype and RNA sequencing data from 1,337 samples from the Genotype-Tissue Expression project. Associations of genetically predicted APA levels with cancer risk were assessed by applying the prediction models to data from large genome-wide association studies of six common cancers among European ancestry populations: breast, ovarian, prostate, colorectal, lung, and pancreatic cancers. A total of 58 risk genes (corresponding to 76 APA sites) were associated with at least one type of cancer, including 25 genes previously not linked to cancer susceptibility. Of the identified risk APAs, 97.4% and 26.3% were supported by 3′-UTR APA quantitative trait loci and colocalization analyses, respectively. Luciferase reporter assays for four selected putative regulatory 3′-UTR variants demonstrated that the risk alleles of 3′-UTR variants, rs324015 (STAT6), rs2280503 (DIP2B), rs1128450 (FBXO38), and rs145220637 (LDHA), significantly increased the posttranscriptional activities of their target genes compared with reference alleles. Furthermore, knockdown of the target genes confirmed their ability to promote proliferation and migration. Overall, this study provides insights into the role of APA in the genetic susceptibility to common cancers.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cancer Research

ISSN

0008-5472

e-ISSN

1538-7445

Volume of the periodical

84

Issue of the periodical within the volume

16

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

2707-2719

UT code for WoS article

001291894000003

EID of the result in the Scopus database

2-s2.0-85201437774