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Updated: Aug 25, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
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Zinc Fingers and Homeobox Family in Cancer: A Double-Edged Sword
Yonghua Bao1, Haifeng Zhang1, Zhixue Han1
1Department of Pathology, Mudanjiang Medical University, Mudanjiang 157011, China.
Abstract:
The zinc fingers and homeobox (ZHX) family includes ZHX1, ZHX2, and ZHX3, and their proteins have similar unique structures, containing two C2H2-type zinc finger motifs and four or five HOX-like homeodomains. The members of the ZHX family can form homodimers or heterodimers with each other or with a subunit of nuclear factor Y. Previous studies have suggested that ZHXs can function as positive or negative transcriptional regulators. Recent studies have further revealed their biological functions and underlying mechanisms in cancers. This review summarized the advances of ZHX-mediated functions, including tumor-suppressive and oncogenic functions in cancer formation and progression, the molecular mechanisms, and regulatory functions, such as cancer cell proliferation, migration, invasion, and metastasis. Moreover, the differential expression levels and their association with good or poor outcomes in patients with various malignancies and differential responses to chemotherapy exert opposite functions of oncogene or tumor suppressors. Therefore, the ZHXs act as a double-edged sword in cancers.
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