Let-7 Status Is Crucial for PARP1 Expression in HER2-Overexpressing Breast Tumors.

ABSTRACT: HER2⁺ breast tumors have been shown to express elevated levels of PARP1 protein. Yet, the mechanism by which PARP1 is upregulated in HER2⁺ breast cancer is unknown. Here, knockdown of HER2 (ERBB2) in HER2⁺ breast cancer cells resulted in a reduction in PARP1 protein. Conversely, ectopic overexpression of HER2 in a non-HER2-overexpressing cell line resulted in increased PARP1 protein levels. Alterations in HER2 expression had no significant effect on PARP1 transcript levels. Instead, HER2 mRNA status was inversely correlated with let-7a miRNA levels in breast cancer cells. Ectopic expression of let-7a miRNA resulted in downregulation of PARP1 protein, whereas expression of the let-7a anti-miRNA increased PARP1 protein. Furthermore, luciferase assays demonstr

SUBMITTER: Wielgos ME 

PROVIDER: S-EPMC5334184 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature