SNP rs4971059 Predisposes to Breast Carcinogenesis and Chemoresistance via TRIM46-mediated HDAC1 degradation

ABSTRACT: Identification of the driving force behind malignant transformation holds the promise to combat the relapse and therapeutic resistance of cancer. We report here that the single-nucleotide polymorphism (SNP) rs4971059, one of 65 new breast cancer risk loci identified in a recent genome-wide association study (GWAS), functions as an active enhancer of TRIM46 expression. Recreating the G-to-A polymorphic switch caused by the SNP via CRISPR/Cas9-mediated homologous recombination leads to an overt upregulation of TRIM46. We find that TRIM46 is a ubiquitin ligase that targets histone deacetylase HDAC1 for ubiquitination and degradation, and that the TRIM46-HDAC1 axis regulates a panel of genes, including ones critically involved in DNA replication and repair. Consequently, TRIM46 promotes breast

SUBMITTER: Prof. Yongfeng Shang 

PROVIDER: S-SCDT-EMBOJ-2021-107974 | biostudies-other |

REPOSITORIES: biostudies-other