Novel long noncoding RNA NMR promotes tumor progression via NSUN2 and BPTF in esophageal squamous cell carcinoma

被引:113
作者
Li, Yuan [1 ,2 ]
Li, Jiagen [1 ,2 ]
Luo, Mei [3 ]
Zhou, Chengcheng [1 ,2 ]
Shi, Xuejiao [1 ,2 ]
Yang, Wenhui [4 ,5 ]
Lu, Zhiliang [1 ,2 ]
Chen, Zhaoli [1 ,2 ]
Sun, Nan [1 ,2 ]
He, Jie [1 ,2 ]
机构
[1] Chinese Acad Med Sci, Dept Thorac Surg, Natl Canc Ctr, Canc Hosp, Beijing 100021, Peoples R China
[2] Peking Union Med Coll, Beijing 100021, Peoples R China
[3] Capital Med Univ, Beijing Luhe Hosp, Cent Lab, Beijing, Peoples R China
[4] Shanxi Med Univ, Dept Biochem & Mol Biol, Taiyuan 030001, Shanxi, Peoples R China
[5] Tumor Hosp Shanxi Prov, Taiyuan 030013, Shanxi, Peoples R China
基金
北京市自然科学基金;
关键词
LncRNAs; ESCC; Oncogenesis; Metastasis; Drug resistance; DOWN-REGULATION; POOR-PROGNOSIS; UP-REGULATION; INVASION; CANCER; PROLIFERATION; LNCRNA; ACTIVATION; MIGRATION; METHYLATION;
D O I
10.1016/j.canlet.2018.05.013
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Long noncoding RNAs (lncRNA) have been implicated in cancer but most of them remain largely unstudied. Here, we identified a novel NSUN2 methylated lncRNA (NMR), which was significantly upregulated in esophageal squamous cell carcinoma (ESCC), functioned as a key regulator of ESCC tumor metastasis and drug resistance. Upregulation of NMR correlated with tumor metastasis and indicated poor overall survival in ESCC patients. Functionally, NMR could promote tumor cell migration and invasion, inhibit cisplatin-induced apoptosis and increase drug resistance in ESCC cells. Mechanistically, transcription of NMR could be upregulated by NF-kappa B activation after IL-beta and TNF-alpha treatment. NMR was methylated by NSUN2 and might competitively inhibit methylation of potential mRNAs. NMR could directly bind to chromatin regulator BPTF, and potentially promote MMP3 and MMP10 expression by ERK1/2 pathway through recruiting BPTF to chromatin. Taken together, NMR functions as an oncogenic gene and may serve as new biomarker and therapeutic target in ESCC.
引用
收藏
页码:57 / 66
页数:10
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