ZMIZ2 promotes the development of triple-receptor negative breast cancer

Xiaopan Zou; Yan Liu; Jun Di; Wei Wei; Nobumoto Watanabe; Jiang Li; Xiaomeng Li

doi:10.1186/s12935-021-02393-x

ZMIZ2 promotes the development of triple-receptor negative breast cancer

Cancer Cell Int. 2022 Jan 31;22(1):52. doi: 10.1186/s12935-021-02393-x.

Authors

Xiaopan Zou^{1

2}, Yan Liu¹, Jun Di³, Wei Wei¹, Nobumoto Watanabe⁴, Jiang Li⁵, Xiaomeng Li⁶

Affiliations

¹ The Key Laboratory of Molecular Epigenetic, Institute of Genetics and Cytology, Northeast Normal University, No.5268 Renmin Street, Nanguan District, Changchun, 130024, Jilin, China.
² Breast and Thyroid Surgery, Jilin Province People's Hospital, Changchun, 130021, Jilin, China.
³ Pathological Diagnostic Center, Jilin Province People's Hospital, Changchun, 130021, Jilin, China.
⁴ Bio-Active Compounds Discovery Research Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama, Japan.
⁵ Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, 510180, Guangdong, China. ljiang@gzhmu.edu.cn.
⁶ The Key Laboratory of Molecular Epigenetic, Institute of Genetics and Cytology, Northeast Normal University, No.5268 Renmin Street, Nanguan District, Changchun, 130024, Jilin, China. lixm441@nenu.edu.cn.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Regulatory network; Survival analysis; Triple-receptor negative breast cancer; ZMIZ2.

Abstract

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