Tissue-specific microRNA expression alters cancer susceptibility conferred by a TP53 noncoding variant.

ABSTRACT: A noncoding polymorphism (rs78378222) in TP53, carried by scores of millions of people, was previously associated with moderate risk of brain tumors and other neoplasms. We find a positive association between this variant and soft tissue sarcoma. In sharp contrast, it is protective against breast cancer. We generated a mouse line carrying this variant and found that it accelerates spontaneous tumorigenesis and glioma development, but strikingly, delays mammary tumorigenesis. The variant creates a miR-382-5p targeting site and compromises a miR-325-3p site. Their differential expression results in p53 downregulation in the brain, but p53 upregulation in the mammary gland of polymorphic mice compared to that of wild-type littermates. Thus, this variant is at odds with Li-Fraumeni Syndrome mu

SUBMITTER: Deng Q 

PROVIDER: S-EPMC6838078 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature