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

被引:111
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
相关论文
共 57 条
[1]   Long non-coding RNAs as targets for cytosine methylation [J].
Amort, Thomas ;
Souliere, Marie F. ;
Wille, Alexandra ;
Jia, Xi-Yu ;
Fiegl, Heidi ;
Woerle, Hildegard ;
Micura, Ronald ;
Lusser, Alexandra .
RNA BIOLOGY, 2013, 10 (06) :1003-1009
[2]   Long noncoding RNAs in cancer cells [J].
Bach, Duc-Hiep ;
Leek, Sang Kook .
CANCER LETTERS, 2018, 419 :152-166
[3]   NF-κB addiction and its role in cancer: 'one size does not fit all' [J].
Chaturvedi, M. M. ;
Sung, B. ;
Yadav, V. R. ;
Kannappan, R. ;
Aggarwal, B. B. .
ONCOGENE, 2011, 30 (14) :1615-1630
[4]   Targetable long non-coding RNAs in cancer treatments [J].
Chen, Liang ;
Dzakah, Emmanuel Enoch ;
Shan, Ge .
CANCER LETTERS, 2018, 418 :119-124
[5]   NFAT1 promotes cell motility through MMP-3 in esophageal squamous cell carcinoma [J].
Chen, Peinan ;
Shan, Zhengzheng ;
Zhao, Jianbo ;
Li, Fengke ;
Zhang, Wenqiang ;
Yang, Liankai ;
Huang, Zhuangshi .
BIOMEDICINE & PHARMACOTHERAPY, 2017, 86 :541-546
[6]   Cancer Statistics in China, 2015 [J].
Chen, Wanqing ;
Zheng, Rongshou ;
Baade, Peter D. ;
Zhang, Siwei ;
Zeng, Hongmei ;
Bray, Freddie ;
Jemal, Ahmedin ;
Yu, Xue Qin ;
He, Jie .
CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132
[7]   Upregulation of long noncoding RNA HOTTIP promotes metastasis of esophageal squamous cell carcinoma via induction of EMT [J].
Chen, Xuemei ;
Han, Hongyu ;
Li, Yuqi ;
Zhang, Qiongxia ;
Mo, Kailan ;
Chen, Size .
ONCOTARGET, 2016, 7 (51) :84480-84485
[8]   Long noncoding RNA SPRY4-IT1 promotes esophageal squamous cell carcinoma cell proliferation, invasion, and epithelial-mesenchymal transition [J].
Cui, Fei ;
Wu, Duoguang ;
He, Xiaotian ;
Wang, Wenjian ;
Xi, Jingle ;
Wang, Minghui .
TUMOR BIOLOGY, 2016, 37 (08) :10871-10876
[9]   The Role of BPTF in Melanoma Progression and in Response to BRAF-Targeted Therapy [J].
Dar, Altaf A. ;
Nosrati, Mehdi ;
Bezrookove, Vladimir ;
de Semir, David ;
Majid, Shahana ;
Thummala, Suresh ;
Sun, Vera ;
Tong, Schuyler ;
Leong, Stanley P. L. ;
Minor, David ;
Billings, Paul R. ;
Soroceanu, Liliana ;
Debs, Robert ;
Miller, James R., III ;
Sagebiel, Richard W. ;
Kashani-Sabet, Mohammed .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2015, 107 (05)
[10]   Landscape of transcription in human cells [J].
Djebali, Sarah ;
Davis, Carrie A. ;
Merkel, Angelika ;
Dobin, Alex ;
Lassmann, Timo ;
Mortazavi, Ali ;
Tanzer, Andrea ;
Lagarde, Julien ;
Lin, Wei ;
Schlesinger, Felix ;
Xue, Chenghai ;
Marinov, Georgi K. ;
Khatun, Jainab ;
Williams, Brian A. ;
Zaleski, Chris ;
Rozowsky, Joel ;
Roeder, Maik ;
Kokocinski, Felix ;
Abdelhamid, Rehab F. ;
Alioto, Tyler ;
Antoshechkin, Igor ;
Baer, Michael T. ;
Bar, Nadav S. ;
Batut, Philippe ;
Bell, Kimberly ;
Bell, Ian ;
Chakrabortty, Sudipto ;
Chen, Xian ;
Chrast, Jacqueline ;
Curado, Joao ;
Derrien, Thomas ;
Drenkow, Jorg ;
Dumais, Erica ;
Dumais, Jacqueline ;
Duttagupta, Radha ;
Falconnet, Emilie ;
Fastuca, Meagan ;
Fejes-Toth, Kata ;
Ferreira, Pedro ;
Foissac, Sylvain ;
Fullwood, Melissa J. ;
Gao, Hui ;
Gonzalez, David ;
Gordon, Assaf ;
Gunawardena, Harsha ;
Howald, Cedric ;
Jha, Sonali ;
Johnson, Rory ;
Kapranov, Philipp ;
King, Brandon .
NATURE, 2012, 489 (7414) :101-108