UHRF1 knockdown induces cell cycle arrest and apoptosis in breast cancer cells through the ZBTB16/ANXA7/Cyclin B1 axis  

作　　者：Di Liu Qin Du Yuxuan Zhu Yize Guo Ya Guo 

机构地区：[1]The Comprehensive Breast Care Center,the Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China [2]Department of Radiation Oncology,the Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第11期1633-1643,共11页生物化学与生物物理学报(英文版)

基　　金：This work was supported by the grants from the Science and Technology Project of Shaanxi Province(No.2022SF-496);the Key Research and Development Program of Shaanxi Province(No.2022SF-213);the Funds of the Second Affiliated Hospital of Xi’an Jiaotong University for Scientists(No.RC(GG201807));the Funds of the Second Affiliated Hospital of Xi’an Jiaotong University(Nos.YJ(ZYTS)2019012 and 2020YJ(ZYTS)226);the Xinrui Cancer Research Support Program(No.cphcf-2022-231);The Medical Research Developing Funds(No.KM228009).

摘　　要：Ubiquitin-like containing PHD and RING finger domains 1(UHRF1)is involved in tumorigenicity through DNA methylation in various cancers,including breast cancer.This study aims to investigate the regulatory mechanisms of UHRF1 in breast cancer progression.Herein,we show that UHRF1 is upregulated in breast cancer tissues and cell lines as measured by western blot analysis and immunohistochemistry.Breast cancer cells are transfected with a UHRF1 overexpression plasmid(pcDNA-UHRF1)or short hairpin RNA targeting UHRF1(sh-UHRF1),followed by detection ofcell proliferation,invasion,apoptosis,and cell cycle.UHRF1 overexpression promotes proliferation and invasion and attenuates cell cycle arrest and apoptosis in breast cancer cells,while UHRF1 knockdown shows the opposite effect.Moreover,methylation-specific PCR and ChlP assays indicate that UHRF1 inhibits zinc finger and BTB domain containing 16(ZBTB16)expression by promoting ZBTB16 promoter methylation via the recruitment of DNA methyltransferase 1(DNMT1).Then,a co-IP assay is used to verify the interaction between ZBTB16 and the annexin A7(ANXA7)protein.ZBTB16 promotes ANXA7expression and subsequently inhibits Cyclin B1 expression.Rescue experiments reveal that ZBTB16knockdown reverses the inhibitory effects of UHRF1knockdown on breast cancer cell malignancies and that ANXA7 knockdown abolishes the inhibitory effects of ZBTB16 overexpression on breast cancer cell malignancies.Additionally,UHRF1 knockdown significantly inhibits xenograft tumor growth in vivo.In conclusion,UHRF1 knockdown inhibits proliferation and invasion,induces cell cycle arrest and apoptosis in breast cancer cells via the ZBTB16/ANXA7/Cyclin B1 axis,and reduces xenograft tumor growth in vivo.

关 键 词：breast cancer cell cycle UHRF1 DNA methylation the ZBTB16/ANXA7/Cyclin B1 axis 

分 类 号：R737.9[医药卫生—肿瘤]