Apolipoprotein A-1 downregulation promotes basal-like breast cancer cell proliferation and migration associated with DNA methylation

Oncol Lett. 2024 May 1;28(1):295. doi: 10.3892/ol.2024.14428. eCollection 2024 Jul.

Abstract

Apolipoprotein A-I (APOA1) performs different roles in different subtypes of breast cancer. It is hypothesized to function as a tumor suppressor in basal-like breast cancer (BLBC). However, the specific role of APOA1 in BLBC and its underlying mechanisms remain unknown. The findings of the present study demonstrated a positive correlation between the expression level of APOA1 and the overall survival of patients with BLBC. Ectopic expression of APOA1 effectively inhibits the proliferation and metastasis of BLBC cells in vitro, and these effects are closely related to DNA methylation. To the best of our knowledge, the present study is the first to report increased methylation of the promoter region and decreased methylation of the structural genes of APOA1 in BLBC cells. These alterations resulted in the downregulation of APOA1 expression and suppression of BLBC tumor growth. Collectively, the results of the present study suggested that APOA1 mRNA expression is negatively regulated by DNA methylation in BLBC. Therefore, low expression of APOA1 may be a potential risk biomarker to predict survival in patients with BLBC.

Keywords: DNA methylation; apolipoprotein A-I; basal-like breast cancer; migration; proliferation.

Grants and funding

The present study was supported by the Zhejiang Province Traditional Chinese Medicine Science and Technology Project (grant nos. 2023ZL056, 2023ZL409 and 2024ZR015); the Research Project of Zhejiang Chinese Medical University (grant nos. 2022JKZKTS26, 2022JKJNTZ16, 2022JKJNTZ23, 2022JKJNTZ29 and 2023JKJNTZ10) and Zhejiang Medical and Health Technology Project (grant nos. 2024KY1225, 2024KY1213, 2024KY1201, 2020KY197 and 2019KY344).