LINC00669 insulates the JAK/STAT suppressor SOCS1 to promote nasopharyngeal cancer cell proliferation and invasion
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(2020) 39:166
RESEARCH
Open Access
LINC00669 insulates the JAK/STAT suppressor SOCS1 to promote nasopharyngeal cancer cell proliferation and invasion Xiang Qing1, Guo-lin Tan1, Huo-wang Liu1, Wei Li1, Jin-gang Ai1, Shan-shan Xiong1, Meng-qing Yang2 and Tian-sheng Wang1*
Abstract 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. Keywords: Nasopharyngeal carcinoma, Long non-coding RNA, LINC00669, JAK/STAT, SOCS1, STAT1
Introduction Nasopharyngeal carcinoma (NPC) is one of the most frequent malignant tumors with extremely high occurrence in Southern China, Northern Africa and parts of the Mediterranean basin [1]. Most NPC is moderately sensitive to radiation therapy, which has been the preferred treatment thus far [2]. However, NPC is featured as a type of poor or undifferentiated carcinoma with only * Correspondence: [email protected] 1 Department of Otolaryngology Head and Neck Surgery, The Third Xiangya Hospital, Central South University, Changsha 410013, China Full list of author information is available at the end of the article
41–63% overall survival rate in patients at the advanced stage [3, 4]. Therefore, deeper insights into the molecular mechanisms that underlie NPC development and progression warrant the better therapeutic strategies targeting the disease. Long non-coding RNA (lncRNA) is a class of longer than 200 nucleotides RNA transcripts [5]. Emerging studies have shown that lncRNAs participate in NPC development and progression. For example, maternally expressed gene 3 (MEG3) was identified as a tumor suppressor lncRNA that is downregulated in NPC due to losses of DNA copy numbers and aberrant promoter
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