Oncology Institute, The Affiliated Hospital of Jiangnan University, Wuxi, 214062, China.
Department of Oncological Surgery, The Affiliated Hospital of Jiangnan University, Wuxi, 214062, China.
Cancer Lett. 2019 Mar 1;444:105-115. doi: 10.1016/j.canlet.2018.12.008. Epub 2018 Dec 21.
Our previous study found that mediator complex subunit 19 (Med19) is upregulated and involved in breast cancer tumorigenesis; however, the detailed effects and mechanism of Med19 in breast cancer require further study. In this study, we found that Med19 was obviously elevated in human breast cancer tissues, which was significantly associated with larger tumors, high-grade malignant features and poor prognosis. Furthermore, Med19 enhanced breast cancer cell proliferation, epithelial-mesenchymal transition, invasion and migration in vitro and in vivo. Med19 interacted with epidermal growth factor receptor (EGFR) and increased EGFR expression. Moreover, Med19 activated the EGFR/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway and exerted its oncogenic activity in an EGFR signaling-mediated manner. In addition, Med19 expression was regulated by miR-101-3p and miR-422a. Med19 expression positively correlated with EGFR expression and negatively correlated with miR-101-3p and miR-422a expression in human breast cancer tissues. Med19 mediated the crosstalk between miR-101-3p/miR-422a and the EGFR/MEK/ERK signaling pathway. This study revealed a new miR-101-3p/miR-422a-Med19-EGFR/MEK/ERK axis that plays a significant role in breast cancer progression. These results help elucidate the potential mechanisms of Med19 in human breast cancer progression.
我们之前的研究发现，中介复合物亚基 19（Med19）上调并参与乳腺癌的肿瘤发生；然而，Med19 在乳腺癌中的详细作用和机制需要进一步研究。在这项研究中，我们发现 Med19 在人乳腺癌组织中明显升高，与更大的肿瘤、高级别恶性特征和不良预后显著相关。此外，Med19 在体外和体内增强了乳腺癌细胞的增殖、上皮-间充质转化、侵袭和迁移。Med19 与表皮生长因子受体（EGFR）相互作用并增加 EGFR 的表达。此外，Med19 激活了 EGFR/丝裂原活化蛋白激酶（MEK）/细胞外信号调节激酶（ERK）通路，并以 EGFR 信号转导介导的方式发挥其致癌活性。此外，Med19 的表达受 miR-101-3p 和 miR-422a 的调控。在人乳腺癌组织中，Med19 的表达与 EGFR 的表达呈正相关，与 miR-101-3p 和 miR-422a 的表达呈负相关。Med19 介导了 miR-101-3p/miR-422a 与 EGFR/MEK/ERK 信号通路之间的串扰。本研究揭示了一个新的 miR-101-3p/miR-422a-Med19-EGFR/MEK/ERK 轴在乳腺癌进展中起着重要作用。这些结果有助于阐明 Med19 在人乳腺癌进展中的潜在机制。
