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LINC01638 lncRNA activates MTDH-Twist1 signaling by preventing SPOP-mediated c-Myc degradation in triple-negative breast cancer

Oncogene (2018) | Download Citation


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.

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This study was supported by grants from the National Natural Science Foundation of China: No. 81672616 (GZ), No. 81402196 (GZ), No. 81772961 (HT), No. 81401989 (NL) and No. 81772825 (HL); supported by grants from Guangdong Natural Science Funds for Distinguished Young Scholars: No. 2016A030306003 (GZ) and Guangdong Natural Science Funds: No. 2017A030313867 (GZ); supported by grants from Science and Technology Program of Guangzhou: No. 201710010100 (GZ) and Guangzhou Municipal University Scientific Research project: 1201610027 (GZ).

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Author notes

  1. These authors contributed equally: Liyun Luo, Hailin Tang.


  1. 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

    • Liyun Luo
    • , Li Ling
    • , Nan Li
    • , Xiaoting Jia
    • , Zhijie Zhang
    • , Xiaorong Wang
    • , Lejuan Shi
    • , Jiang Yin
    • , Ni Qiu
    • , Hao Liu
    • , Ying Song
    • , Kai Luo
    • , Hongsheng Li
    • , Zhimin He
    •  & Guopei Zheng
  2. 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

    • Hailin Tang
    •  & Xiaoming Xie


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The authors declare that they have no conflict of interest.

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Correspondence to Guopei Zheng or Xiaoming Xie.

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