Zou Xiaopan, Liu Yan, Di Jun, Wei Wei, Watanabe Nobumoto, Li Jiang, Li Xiaomeng
The Key Laboratory of Molecular Epigenetic, Institute of Genetics and Cytology, Northeast Normal University, No.5268 Renmin Street, Nanguan District, Changchun, 130024, Jilin, China.
Breast and Thyroid Surgery, Jilin Province People's Hospital, Changchun, 130021, Jilin, China.
Cancer Cell Int. 2022 Jan 31;22(1):52. doi: 10.1186/s12935-021-02393-x.
Triple-receptor negative breast cancer (TNBC) is an aggressive breast tumor subtype that generally has a poor prognosis. This study aimed to investigate the role and regulatory mechanisms of Zinc finger MIZ-type containing 2 (ZMIZ2) in relation to TNBC.
Based on data from The Cancer Genome Atlas (TCGA), the expression of ZMIZ2 in different subtypes and its correlation with androgen receptor (AR) were analyzed, and a regulatory mechanism network was constructed. The expression and prognostic value of ZMIZ2 in clinical TNBC tissue samples were also investigated. Furthermore, in vitro studies were conducted to investigate the effects of ZMIZ2 knockdown on the malignant behaviors of TNBC cells and target gene expression.
Based on TCGA data, ZMIZ2 was found to be significantly upregulated in TNBC tissues and its expression was negatively correlated with AR expression. Key relationships, such as the ZMIZ2-CCL5, ZMIZ2/AR-MCM3, ZMIZ2/AR-E2F4, and the ZMIZ2/AR-DHX38 were identified, which were enriched in NOD-like receptor signaling pathway/toll-like receptor signaling pathway, DNA replication, cell cycle, and spliceosome, respectively. Moreover, ZMIZ2 was upregulated in clinical breast cancer tissues and its high expression was correlated with the poor prognosis of TNBC patients. Furthermore, ZMIZ2 expression was increased in breast cancer cells, and a knockdown of ZMIZ2 inhibited MDA-MB-231 cell proliferation, migration, and invasion, induced cell cycle arrest in the G1 phase, and promoted cell apoptosis. Furthermore, ZMIZ2 knockdown inhibited the mRNA and protein expression of CCL5, MCM3, E2F4, and DHX38.
Our findings reveal that ZMIZ2 is upregulated in TNBC tissues and is associated with its poor prognosis. ZMIZ2 may promote TNBC progression by promoting the expression of its target genes and affecting the corresponding pathways. Consequently, ZMIZ2 may serve as a promising target for future TNBC treatments.
三受体阴性乳腺癌（TNBC）是一种侵袭性乳腺癌亚型，通常预后较差。本研究旨在探讨含锌指MIZ型2（ZMIZ2）在TNBC中的作用及其调控机制。
基于癌症基因组图谱（TCGA）的数据，分析ZMIZ2在不同亚型中的表达及其与雄激素受体（AR）的相关性，并构建调控机制网络。还研究了ZMIZ2在临床TNBC组织样本中的表达及预后价值。此外，进行了体外研究以探讨ZMIZ2敲低对TNBC细胞恶性行为和靶基因表达的影响。
基于TCGA数据，发现ZMIZ2在TNBC组织中显著上调，其表达与AR表达呈负相关。确定了关键关系，如ZMIZ2-CCL5、ZMIZ2/AR-MCM3、ZMIZ2/AR-E2F4和ZMIZ2/AR-DHX38，它们分别富集于NOD样受体信号通路/Toll样受体信号通路、DNA复制、细胞周期和剪接体。此外，ZMIZ2在临床乳腺癌组织中上调，其高表达与TNBC患者的不良预后相关。此外，乳腺癌细胞中ZMIZ2表达增加，敲低ZMIZ2可抑制MDA-MB-231细胞的增殖、迁移和侵袭，诱导细胞周期停滞在G1期，并促进细胞凋亡。此外，ZMIZ2敲低抑制了CCL5、MCM3、E2F4和DHX38的mRNA和蛋白表达。
我们的研究结果表明，ZMIZ2在TNBC组织中上调，并与其不良预后相关。ZMIZ2可能通过促进其靶基因的表达并影响相应途径来促进TNBC的进展。因此，ZMIZ2可能成为未来TNBC治疗的一个有前景的靶点。
