Posttranscriptional upregulation of HER3 by HER2 mRNA induces trastuzumab resistance in breast cancer.

ABSTRACT:

Background

HER2 gene amplification generates an enormous number of HER2 transcripts, but the global effects on endogenous miRNA targets including HER family members in breast cancer are unexplored.

Methods

We generated a HER2-3'UTR expressing vector to test the tumor-promoting properties in HER2 low expressing T47D and MCF7 cells. Through microarray analysis and real-time PCR analysis we identified genes that were regulated by HER2-3'UTR. Positive and negative manipulation of miRNA expression, response element mutational studies and transcript reporter assays were performed to explore the mechanism of competitive sequestration of miR125a/miRNA125b by HER2 3'UTR. To investigate if trastuzumab-induced upregulation of HER3 is also mediated through miRNA de-repression, we used t

SUBMITTER: Li X 

PROVIDER: S-EPMC6090962 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature