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

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 main...

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Bibliographic Details
Published in:Oncogene 2018-11, Vol.37 (47), p.6166-6179
Main Authors: Luo, Liyun, Tang, Hailin, Ling, Li, Li, Nan, Jia, Xiaoting, Zhang, Zhijie, Wang, Xiaorong, Shi, Lejuan, Yin, Jiang, Qiu, Ni, Liu, Hao, Song, Ying, Luo, Kai, Li, Hongsheng, He, Zhimin, Zheng, Guopei, Xie, Xiaoming
Format: Article
Language:English
Subjects:
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Apoptosis
Breast cancer
c-Myc protein
Cancer metastasis
Cancer patients
Care and treatment
Cell Biology
Cellular proteins
Cellular signal transduction
Development and progression
Gene expression
Genetic aspects
Health
Health aspects
Human Genetics
Internal Medicine
Medicine
Medicine & Public Health
Mesenchyme
Metastases
Myc protein
Oncology
Signal transduction
Stem cells
Transcription
Triple negative breast cancer
Tumors
Ubiquitin
Ubiquitination
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Summary: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.
ISSN:0950-9232
1476-5594
DOI:10.1038/s41388-018-0396-8