BMI1 promotes the proliferation and inhibits autophagy of breast cancer cells by activating COPZ1.

This study was designed to explore the role of COPZ1 in breast cancer as well as discuss its specific reaction mechanism. With the help of RT-qPCR and western blot, the expression of BMI1 and COPZ1 were measured. Then, the proliferation, colony formation and apoptosis were evaluated by CCK-8, colony formation and TUNEL assays, separately. Luciferase reporter assay and ChIP were applied to assess the relative activity of COPZ1 promoter as well as its binding with BMI1. Moreover, western blot was utilized to measure the expression of proliferation-, apoptosis- and autophagy-related proteins. According to GEPIA2 database, COPZ1 was upregulated in breast cancer tissues and was associated with the poor prognosis (P = 0.03). Results obtained from RT-qPCR and western blot verified that COPZ1 expression was greatly increased at both mRNA and protein levels in breast cancer cells as compared to control cells (P < 0.05 or P < 0.001). COPZ1 knockdown inhibited the proliferation, induced the autophagy and promoted the apoptosis of breast cancer cells. HumanTFDB predicted the binding sites of BMI1 and COPZ1. The increased relative luciferase activity of COPZ1 promoter following BMI1 overexpression (P < 0.001) and the binding of BMI1 with COPZ1 promoter indicated that BMI1 could activate COPZ1. Further experiments suggested that the effects of COPZ1 knockdown on the proliferation, apoptosis and autophagy of breast cancer cells were reversed by BMI1 overexpression, implying that BMI1 promoted the proliferation and repressed the autophagy of breast cancer cells via activating COPZ1. To sum up, BMI1 exhibited promotive effects on the malignant progression of breast cancer through the activation of COPZ1. These findings might offer a preliminary theoretical basis for COPZ1 participation in autophagy in breast cancer cells. © 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).

Citation

Shuming Chen, He Li, Siyu Chen, Bing Wang, Kaixiang Zhang. BMI1 promotes the proliferation and inhibits autophagy of breast cancer cells by activating COPZ1. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2022 Nov;24(11):2166-2174

PMID: 35789980

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