MIER3 induces epithelial-mesenchymal transition and promotes breast cancer cell aggressiveness via forming a co-repressor complex with HDAC1/HDAC2/Snail
MIER3 induces epithelial-mesenchymal transition and promotes breast cancer cell aggressiveness via forming a co-repressor complex with HDAC1/HDAC2/Snail
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DOI：
10.1016/j.yexcr.2021.112722
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发表时间：
2021-07-13
影响因子：
3.7
通讯作者：
Zhou, Jun
中科院分区：
文献类型：
--
作者：
Huang, Wenqing;Chen, Jianxiong;Zhou, Jun
乳腺癌是最常见的癌症之一，也是女性癌症死亡的主要原因。MIER3(中胚层诱导早期反应1，家族成员3)被认为是乳腺癌的潜在致癌基因。然而，MIER3在乳腺癌中的作用在很大程度上仍不清楚。检测MIER3的表达，并分析其表达与临床病理特征的关系。体外和体内检测MIER3对乳腺癌细胞增殖和迁移的影响。用Western印迹、IF和Co-IP检测MIER3、HDAC1、HDAC2与蜗牛的关系。芯片法检测MIER3/HDAC1/HDAC2/Snail复合体与E-钙粘蛋白启动子的结合情况。在本研究中，我们发现MIER3在乳腺癌组织中表达上调，并与患者预后不良密切相关。MIER3可促进乳腺癌细胞的增殖、迁移和上皮-间充质转化。进一步研究表明，MIER3与HDAC1/HDAC2和Snail相互作用形成抑制复合体，该复合体可与E-钙粘蛋白启动子结合，并与其脱乙酰基有关。我们的研究结论是，MIER3参与了与HDAC1/HDAC2/Snail形成共抑制物复合体，通过沉默E-钙粘素来促进EMT。
Breast cancer is one of the most frequently diagnosed cancers and the leading cause of cancer death in women. MIER3 (Mesoderm induction early response 1, family member3) is considered as a potential oncogene for breast cancer. However, the role of MIER3 in breast cancer remain largely unknown. The expression of MIER3 was detected and the relationship between its expression and clinicopathological characteristics was also analyzed. The effect of MIER3 on proliferation and migration of breast cancer cells was detected in vitro and in vivo. Western blot, IF, and Co-IP were employed to detect the relationship between MIER3, HDAC1, HDAC2, and Snail. ChIP assay was performed to determine the binding of MIER3/HDAC1/HDAC2/Snail complex to the promoter of E-cadherin. In this study, we found that MIER3 was upregulated in breast cancer tissue and closely associated with poor prognosis of patients. MIER3 could promote the proliferation, migration, and epithelial-mesenchymal transition (EMT) of breast cancer cells. Further studies showed that MIER3 interacted with HDAC1/HDAC2 and Snail to form a repressive complex which could bind to E-cadherin promoter and was related to its deacetylation. Our study concluded that MIER3 was involved in forming a co-repressor complex with HDAC1/HDAC2/Snail to promote EMT by silencing E-cadherin.