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.

中文翻译：

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LINC01638 lncRNA通过防止三阴性乳腺癌中SPOP介导的c-Myc降解来激活MTDH-Twist1信号传导。

乳腺癌是一种异质性疾病，三阴性乳腺癌（TNBC）仍然是严重的健康问题。lncRNA在TNBC进程中的潜在参与尚待探索。在这里，我们证明了LINC01638在TNBC组织和细胞中高度表达。LINC01638维持TNBC细胞的间质特征，包括丰富的上皮-间质转化（EMT）标记和癌干细胞样状态。LINC01638抑制在体外和体内均抑制肿瘤增殖和转移。LINC01638过表达预测乳腺癌患者的预后不良。从机理上讲，LINC01638与c-Myc相互作用以防止SPOP介导的c-Myc泛素化和降解。C-Myc转录增强MTDH（metadherin）表达，并随后激活Twist1表达以诱导EMT。