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CYB561 promotes HER2+ breast cancer proliferation by inhibiting H2AFY degradation

  • Ting Zhao,
  • Chaomin Wang,
  • Na Zhao,
  • Ge Qiao,
  • Jialei Hua,
  • Donghua Meng,
  • Liming Liu,
  • Benfu Zhong,
  • Miao Liu,
  • Yichao Wang,
  • Changsen Bai,
  • Yueguo Li

摘要

Breast cancer (BRCA) has a high incidence and mortality rate among women. Different molecular subtypes of breast cancer have different prognoses and require personalized therapies. It is imperative to find novel therapeutic targets for different molecular subtypes of BRCA. Here, we demonstrated for the first time that Cytochromeb561 (CYB561) is highly expressed in BRCA and correlates with poor prognosis, especially in HER2-positive BRCA. Overexpression of CYB561 could upregulate macroH2A (H2AFY) expression in HER2-positive BRCA cells through inhibition of H2AFY ubiquitination, and high expression of CYB561 in HER2-positive BRCA cells could promote the proliferation and migration of cells. Furthermore, we have demonstrated that CYB561 regulates H2AFY expression, thereby influencing the expression of NF-κB, a downstream molecule of H2AFY. These findings have been validated through in vivo experiments. In conclusion, we propose that CYB561 may represent a novel therapeutic target for the treatment of HER2-positive BRCA.