Low plasma levels of miR-101 are associated with tumor progression in gastric cancer

被引:44
作者
Imamura, Taisuke [1 ]
Komatsu, Shuhei [1 ]
Ichikawa, Daisuke [1 ]
Miyamae, Mahito [1 ]
Okajima, Wataru [1 ]
Ohashi, Takuma [1 ]
Kiuchi, Jun [1 ]
Nishibeppu, Keiji [1 ]
Kosuga, Toshiyuki [1 ]
Konishi, Hirotaka [1 ]
Shiozaki, Atsushi [1 ]
Okamoto, Kazuma [1 ]
Fujiwara, Hitoshi [1 ]
Otsuji, Eigo [1 ]
机构
[1] Kyoto Prefectural Univ Med, Dept Surg, Div Digest Surg, Kamigyo Ku, Kyoto 6028566, Japan
关键词
gastric cancer; tumor suppressor microRNA; plasma; biomarker; MICRORNA PROFILES IDENTIFICATION; CIRCULATING MICRORNAS; DOWN-REGULATION; CYCLOOXYGENASE-2; OVEREXPRESSION; HEPATOCELLULAR-CARCINOMA; CLINICAL IMPACT; BIOMARKER; GROWTH; CELLS; EZH2;
D O I
10.18632/oncotarget.20860
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Several studies have identified the decreased expression of the tumor suppressor miR-101 in various cancers. In this study, we tested miR-101 as a potential therapeutic target and novel plasma biomarker for gastric cancer (GC). Results: The miR-101 expression level was significantly lower in GC tissues (P = 0.0038) and GC cell lines (P = 0.0238) than in normal gastric mucosa. Both exosomal and plasma miR-101 were significantly downregulated in GC patients compared with healthy volunteers (P = 0.0281 and P < 0.0001, respectively). Low miR-101 plasma level was significantly associated with advanced T factor, advanced disease stage, and peritoneal metastasis and predicted poor prognosis in GC patients (P = 0.0368; hazard ratio, 3.079; 95% confidence interval: 1.06-11.08). Overexpression of miR-101 in GC cells induced apoptosis by inhibiting MCL1 and suppressed cell migration and invasion by regulating ZEB1. Conclusions: Depletion of the tumor suppressor miRNA-101 in plasma is related to tumor progression and poor outcomes. Low plasma miR-101 may be a biomarker for GC, and its restoration might be a novel anticancer treatment strategy.
引用
收藏
页码:106538 / 106550
页数:13
相关论文
共 64 条
[1]   Understanding diagnostic tests 3: receiver operating characteristic curves [J].
Akobeng, Anthony K. .
ACTA PAEDIATRICA, 2007, 96 (05) :644-647
[2]   Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma [J].
Arroyo, Jason D. ;
Chevillet, John R. ;
Kroh, Evan M. ;
Ruf, Ingrid K. ;
Pritchard, Colin C. ;
Gibson, Donald F. ;
Mitchell, Patrick S. ;
Bennett, Christopher F. ;
Pogosova-Agadjanyan, Era L. ;
Stirewalt, Derek L. ;
Tait, Jonathan F. ;
Tewari, Muneesh .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (12) :5003-5008
[3]   The tumor suppressor gene rap1GAP is silenced by miR-101-mediated EZH2 overexpression in invasive squamous cell carcinoma [J].
Banerjee, R. ;
Mani, R-S ;
Russo, N. ;
Scanlon, C. S. ;
Tsodikov, A. ;
Jing, X. ;
Cao, Q. ;
Palanisamy, N. ;
Metwally, T. ;
Inglehart, R. C. ;
Tomlins, S. ;
Bradford, C. ;
Carey, T. ;
Wolf, G. ;
Kalyana-Sundaram, S. ;
Chinnaiyan, A. M. ;
Varambally, S. ;
D'Silva, N. J. .
ONCOGENE, 2011, 30 (42) :4339-4349
[4]  
Bang YJ, 2010, LANCET, V376, P1302
[5]   MicroRNA signatures in human cancers [J].
Calin, George A. ;
Croce, Carlo M. .
NATURE REVIEWS CANCER, 2006, 6 (11) :857-866
[6]   Lack of microRNA-101 causes E-cadherin functional deregulation through EZH2 up-regulation in intestinal gastric cancer [J].
Carvalho, Joana ;
van Grieken, Nicole C. ;
Pereira, Patricia M. ;
Sousa, Sonia ;
Tijssen, Marianne ;
Buffart, Tineke E. ;
Diosdado, Begona ;
Grabsch, Heike ;
Santos, Manuel A. S. ;
Meijer, Gerrit ;
Seruca, Raquel ;
Carvalho, Beatriz ;
Oliveira, Carla .
JOURNAL OF PATHOLOGY, 2012, 228 (01) :31-44
[7]   Long non-coding RNA XIST regulates gastric cancer progression by acting as a molecular sponge of miR-101 to modulate EZH2 expression [J].
Chen, Dong-liang ;
Ju, Huai-qiang ;
Lu, Yun-xin ;
Chen, Le-zong ;
Zeng, Zhao-lei ;
Zhang, Dong-sheng ;
Luo, Hui-yan ;
Wang, Feng ;
Qiu, Miao-zhen ;
Wang, De-shen ;
Xu, Da-zhi ;
Zhou, Zhi-wei ;
Pelicano, Helene ;
Huang, Peng ;
Xie, Dan ;
Wang, Feng-hua ;
Li, Yu-hong ;
Xu, Rui-hua .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2016, 35
[8]   Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases [J].
Chen, Xi ;
Ba, Yi ;
Ma, Lijia ;
Cai, Xing ;
Yin, Yuan ;
Wang, Kehui ;
Guo, Jigang ;
Zhang, Yujing ;
Chen, Jiangning ;
Guo, Xing ;
Li, Qibin ;
Li, Xiaoying ;
Wang, Wenjing ;
Zhang, Yan ;
Wang, Jin ;
Jiang, Xueyuan ;
Xiang, Yang ;
Xu, Chen ;
Zheng, Pingping ;
Zhang, Juanbin ;
Li, Ruiqiang ;
Zhang, Hongjie ;
Shang, Xiaobin ;
Gong, Ting ;
Ning, Guang ;
Wang, Jun ;
Zen, Ke ;
Zhang, Junfeng ;
Zhang, Chen-Yu .
CELL RESEARCH, 2008, 18 (10) :997-1006
[9]   Shedding microvesicles: artefacts no more [J].
Cocucci, Emanuele ;
Racchetti, Gabriella ;
Meldolesi, Jacopo .
TRENDS IN CELL BIOLOGY, 2009, 19 (02) :43-51
[10]   Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? [J].
Filipowicz, Witold ;
Bhattacharyya, Suvendra N. ;
Sonenberg, Nahum .
NATURE REVIEWS GENETICS, 2008, 9 (02) :102-114