LINC00669 insulates the JAK/STAT suppressor SOCS1 to promote nasopharyngeal cancer cell proliferation and invasion

Autor: Meng-qing Yang, Shan-shan Xiong, Wei Li, Xiang Qing, Jingang Ai, Tiansheng Wang, Huowang Liu, Guolin Tan
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Cancer Research
Apoptosis
law.invention
Mice
0302 clinical medicine
STAT1
Transcription (biology)
law
Cell Movement
Tumor Cells
Cultured
SOCS1
Mice
Inbred BALB C
biology
JAK-STAT signaling pathway
Prognosis
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Long non-coding RNA
Gene Expression Regulation
Neoplastic
Survival Rate
STAT1 Transcription Factor
Oncology
030220 oncology & carcinogenesis
RNA
Long Noncoding
Mice
Nude
lcsh:RC254-282
03 medical and health sciences
Suppressor of Cytokine Signaling 1 Protein
medicine
Biomarkers
Tumor
Nasopharyngeal carcinoma
Animals
Humans
Neoplasm Invasiveness
Cell Proliferation
Suppressor of cytokine signaling 1
Research
Nasopharyngeal Neoplasms
Janus Kinase 1
medicine.disease
Xenograft Model Antitumor Assays
JAK/STAT
LINC00669
030104 developmental biology
Cancer cell
biology.protein
Cancer research
Suppressor
Zdroj: Journal of Experimental & Clinical Cancer Research, Vol 39, Iss 1, Pp 1-16 (2020)
Journal of Experimental & Clinical Cancer Research : CR
ISSN: 1756-9966
DOI: 10.1186/s13046-020-01674-z
Popis: Nasopharyngeal carcinoma (NPC) is an epithelial cancer emerging from the lining of nasopharyngeal mucosa, with extremely frequent occurrence in east and southeast Asia. For the purpose of exploring roles of the dysregulated long non-coding RNA (lncRNA) in NPC, we identified a novel lncRNA LINC00669 with an apparent negative correlation to the overall survival from human NPC mRNA expression profiling databases. We further performed RNA pulldown coupled with mass spectrum to find out its target protein, and applied a series of in vitro and in vivo loss-and-gain-of function assays to investigate its oncogenic roles in NPC tumor development and progression. Our results demonstrated that LINC00669 competitively binds to the key JAK/STAT signaling pathway suppressor SOCS1, and insulates it from imposing ubiquitination modification on the pathway component of STAT1, which leads to its abnormal stabilization and activation. The activated STAT1 is then transferred into the nucleus and initiates the transcription of genes related to proliferation and invasion. In summary, our study reveals that the cytoplasmic resident lncRNA LINC00669 confers malignant properties on NPC cancer cells by facilitating a persistent activation of the JAK/STAT signaling pathway. Findings in the current study shed lights on prospects for treating NPC using strategies targeting the novel regulator of the JAK/STAT signaling.
Databáze: OpenAIRE
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