| HRA001206
(Controlled Access)
|
Circular HER2 RNA (circHER2) encoded a novel protein, HER2_103. Unexpectedly, while HER2 mRNA and protein were barely detected, circ_HER2/HER2_103 was expressed in about 30% TNBC clinical samples. Circ_HER2/HER2_103 positive TNBC patients harbored worse overall prognosis than circ_HER2/HER2_103 negative patients.Knockdown circ_HER2 inhibited TNBC cells proliferation, invasion and tumorigenesis in vitro and in vivo, suggesting the critical role of circ_HER2/HER2_103 in TNBC tumorigenicity. Mechanistically, HER2_103 promoted homo/hetero dimerization of epidermal growth factor receptor (EGFR)/HER3, sustained AKT phosphorylation and downstream malignant phenotypes. Furthermore, HER2_103 shared most of the same amino acid sequences as HER2 CR1 domain which could be antagonized by Pertuzumab, a clinical used HER2 antibody. Pertuzumab markedly attenuated in vivo tumorigenicity of circ_HER2/HER2_103 expressing TNBC cells but showed no effects in circ_HER2/HER2_103 negative TNBC cells. |
