LINC01638 lncRNA 通过阻止 SPOP 介导的 c-Myc 降解激活三阴性乳腺癌中的 MTDH-Twist1 信号通路。
LINC01638 lncRNA activates MTDH-Twist1 signaling by preventing SPOP-mediated c-Myc degradation in triple-negative breast cancer.
机构信息
Affiliated Cancer Hospital & Institute of Guangzhou Medical University; Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment"; Protein Modification and Degradation Lab, Guangzhou Medical University, Hengzhigang Road 78#, 510095, Guangzhou, Guangdong, China.
Department of Breast Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Dongfeng Road 651 E, 510060, Guangzhou, Guangdong, China.
出版信息
Oncogene. 2018 Nov;37(47):6166-6179. doi: 10.1038/s41388-018-0396-8. Epub 2018 Jul 12.
Breast cancer is a heterogeneous disease, and triple-negative breast cancer (TNBC) continues to be a serious health problem. The potential involvement of lncRNAs in TNBC progression remains unexplored. Here, we demonstrated that LINC01638 is highly expressed in TNBC tissues and cells. LINC01638 maintains the mesenchymal traits of TNBC cells, including an enriched epithelial-mesenchymal transition (EMT) signature and cancer stem cell-like state. LINC01638 knockdown suppresses tumor proliferation and metastasis both in vitro and in vivo. LINC01638 overexpression predicts a poor outcome of breast cancer patients. Mechanistically, LINC01638 interacts with c-Myc to prevent SPOP-mediated c-Myc ubiquitination and degradation. C-Myc transcriptionally enhances MTDH (metadherin) expression and subsequently activates Twist1 expression to induce EMT. Our findings describe LINC01638-mediated signal transduction and highlight the crucial role of LINC01638 in TNBC progression.
乳腺癌是一种异质性疾病，三阴性乳腺癌（TNBC）仍然是一个严重的健康问题。lncRNAs 潜在参与 TNBC 进展仍未被探索。在这里，我们证明 LINC01638 在 TNBC 组织和细胞中高表达。LINC01638 维持 TNBC 细胞的间质特征，包括富含上皮-间充质转化（EMT）特征和癌症干细胞样状态。LINC01638 敲低抑制 TNBC 细胞的体外和体内增殖和转移。LINC01638 的过表达预示着乳腺癌患者的预后不良。在机制上，LINC01638 与 c-Myc 相互作用，防止 SPOP 介导的 c-Myc 泛素化和降解。c-Myc 转录增强 MTDH（metadherin）的表达，并随后激活 Twist1 的表达，诱导 EMT。我们的研究结果描述了 LINC01638 介导的信号转导，并强调了 LINC01638 在 TNBC 进展中的关键作用。
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