Yu Zi-Han, Lun Shu-Min, He Rui, Tian Hong-Pan, Huang Huan-Jing, Wang Qing-Shan, Li Xiao-Qing, Feng Yu-Mei
Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China.
Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China; Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China.
Cancer Lett. 2017 Aug 28;402:142-152. doi: 10.1016/j.canlet.2017.05.020. Epub 2017 May 31.
Myc-associated zinc finger protein (MAZ) is a transcription factor with C2H2-type zinc-finger motifs that can bind GC-rich cis-elements. MAZ activates the transcription of some cancer-related genes and represses that of others, suggesting that changes in MAZ expression may play different roles in the development and progression of different types or subtypes of cancers depending on its target genes. However, the functions and mechanisms of MAZ in regulating the carcinogenesis and progression of breast cancer have remained unclear. In the current study, we show that MAZ performs dual function in basal-like breast cancer (BLBC): suppression of aggressiveness and promotion of proliferation. Forkhead box F2 (FOXF2) is a novel transcription target of MAZ and mediates the functions of MAZ. The MAZ mRNA level, particularly in combination with the FOXF2 mRNA level, may serve as a prognostic marker for BLBC patients. Our results indicate that the dual function of the MAZ-FOXF2 axis reflect the pleiotropic nature of multifunctional transcription factors in regulating the different stages of cancer development and progression, which could lead to the complexity of cancer diagnosis and treatment.
Myc相关锌指蛋白（MAZ）是一种具有C2H2型锌指基序的转录因子，能够结合富含GC的顺式元件。MAZ可激活某些癌症相关基因的转录，同时抑制其他一些基因的转录，这表明MAZ表达的变化可能因其靶基因的不同，在不同类型或亚型癌症的发生发展过程中发挥不同作用。然而，MAZ在调控乳腺癌发生发展中的功能及机制仍不清楚。在本研究中，我们发现MAZ在基底样乳腺癌（BLBC）中发挥双重作用：抑制侵袭性并促进增殖。叉头框F2（FOXF2）是MAZ的一个新的转录靶点，并介导MAZ的功能。MAZ mRNA水平，特别是与FOXF2 mRNA水平相结合，可能作为BLBC患者的预后标志物。我们的结果表明，MAZ - FOXF2轴的双重功能反映了多功能转录因子在调控癌症发展和进展不同阶段的多效性，这可能导致癌症诊断和治疗的复杂性。
