Expression, regulation and roles of miR-26a and MEG3 in tongue squamous cell carcinoma

被引:194
作者
Jia, Ling-Fei [1 ]
Wei, Su-Bi [2 ]
Gan, Ye-Hua [3 ]
Guo, Yong [2 ]
Gong, Kai [4 ]
Mitchelson, Keith [2 ]
Cheng, Jing [2 ]
Yu, Guang-Yan [1 ]
机构
[1] Peking Univ, Dept Oral & Maxillofacial Surg, Sch & Hosp Stomatol, Beijing 100081, Peoples R China
[2] Tsinghua Univ, Med Syst Biol Res Ctr, Beijing 100084, Peoples R China
[3] Peking Univ, Mol Biol Lab, Sch & Hosp Stomatol, Beijing 100081, Peoples R China
[4] Tsinghua Univ, Sch Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China
关键词
miR-26a; lncRNA; MEG3; DNMT3B; squamous cell carcinoma; LONG NONCODING RNA; HEPATOCELLULAR-CARCINOMA; MICRORNA EXPRESSION; BREAST-CANCER; LIVER-CANCER; EZH2; APOPTOSIS; PATHWAY; GROWTH; GENE;
D O I
10.1002/ijc.28667
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MicroRNA miR-26a and long noncoding RNA (lncRNA) MEG3 gene have been independently reported to be tumor suppressor genes in various cancers, but neither has been previously associated with tongue squamous cell carcinoma (TSCC). We report here that miR-26a and lncRNA MEG3 gene expression were both strongly reduced in TSCC compared with levels in matched nonmalignant tissues, and combined low expression levels of both miR-26a and MEG3 emerged as an independent prognostic factor for poor clinical outcome in TSCC patients. Assays in the human TSCC cell lines SCC-15 and CAL27 showed that miR-26a targets the DNA methyltransferase 3B transcript and that its inhibition may result in the upregulation of MEG3, providing a plausible link between the observed reduction of miR-26a and MEG3 in TSCC tissue. Furthermore, the overexpression of miR-26a or MEG3 in SCC-15 and CAL27 cells inhibited cell proliferation and cell cycle progression, and promoted cell apoptosis. Considering the poor prognostic outcomes associated with reduced miR-26a and MEG3, our findings imply that these factors likely play important antitumor effects in TSCC pathogenesis. Furthermore, they represent potential prognostic biomarkers for stratification of TSCC patients.
引用
收藏
页码:2282 / 2293
页数:12
相关论文
共 48 条
[1]  
[Anonymous], 2011, TNM CLASSIFICATION M
[2]   Tongue cancer: Is there a difference in survival compared with other subsites in the oral cavity? [J].
Bell, R. Bryan ;
Kademani, Deepak ;
Homer, Louis ;
Dierks, Eric J. ;
Potter, Bryce E. .
JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY, 2007, 65 (02) :229-236
[3]   CpG methylation analysis of the MEG3 and SNRPN imprinted genes in acute myeloid leukemia and myelodysplastic syndromes [J].
Benetatos, Leonidas ;
Hatzimichael, Eleftheria ;
Dasoula, Aggeliki ;
Dranitsaris, George ;
Tsiara, Stavroula ;
Syrrou, Maria ;
Georgiou, Ioannis ;
Bourantas, Konstantinos L. .
LEUKEMIA RESEARCH, 2010, 34 (02) :148-153
[4]   microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer [J].
Braconi, C. ;
Kogure, T. ;
Valeri, N. ;
Huang, N. ;
Nuovo, G. ;
Costinean, S. ;
Negrini, M. ;
Miotto, E. ;
Croce, C. M. ;
Patel, T. .
ONCOGENE, 2011, 30 (47) :4750-4756
[5]   Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers [J].
Brunner, Alayne L. ;
Beck, Andrew H. ;
Edris, Badreddin ;
Sweeney, Robert T. ;
Zhu, Shirley X. ;
Li, Rui ;
Montgomery, Kelli ;
Varma, Sushama ;
Gilks, Thea ;
Guo, Xiangqian ;
Foley, Joseph W. ;
Witten, Daniela M. ;
Giacomini, Craig P. ;
Flynn, Ryan A. ;
Pollack, Jonathan R. ;
Tibshirani, Robert ;
Chang, Howard Y. ;
van de Rijn, Matt ;
West, Robert B. .
GENOME BIOLOGY, 2012, 13 (08) :R75
[6]   Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses [J].
Cabili, Moran N. ;
Trapnell, Cole ;
Goff, Loyal ;
Koziol, Magdalena ;
Tazon-Vega, Barbara ;
Regev, Aviv ;
Rinn, John L. .
GENES & DEVELOPMENT, 2011, 25 (18) :1915-1927
[7]   Ultraconserved regions encoding ncRNAs are, altered in human leukemias and carcinomas [J].
Calin, George A. ;
Liu, Chang-Gong ;
Ferracin, Manuela ;
Hyslop, Terry ;
Spizzo, Riccardo ;
Sevignani, Cinzia ;
Fabbri, Muller ;
Cimmino, Amelia ;
Lee, Eun Joo ;
Wojcik, Sylwia E. ;
Shimizu, Masayoshi ;
Tili, Esmerina ;
Rossi, Simona ;
Taccioli, Cristian ;
Pichiorri, Flavia ;
Liu, Xiuping ;
Zupo, Simona ;
Herlea, Vlad ;
Gramantieri, Laura ;
Lanza, Giovanni ;
Alder, Hansjuerg ;
Rassenti, Laura ;
Volinia, Stefano ;
Schmittgen, Thomas D. ;
Kipps, Thomas J. ;
Negrini, Massimo ;
Croce, Carlo M. .
CANCER CELL, 2007, 12 (03) :215-229
[8]   Real-time quantification of microRNAs by stem-loop RT-PCR [J].
Chen, CF ;
Ridzon, DA ;
Broomer, AJ ;
Zhou, ZH ;
Lee, DH ;
Nguyen, JT ;
Barbisin, M ;
Xu, NL ;
Mahuvakar, VR ;
Andersen, MR ;
Lao, KQ ;
Livak, KJ ;
Guegler, KJ .
NUCLEIC ACIDS RESEARCH, 2005, 33 (20) :e179.1-e179.9
[9]   Deregulated expression of miR-26a and Ezh2 in rhabdomyosarcoma [J].
Ciarapica, Roberta ;
Russo, Guiseppe ;
Verginelli, Federica ;
Raimondi, Lavinia ;
Donfrancesco, Alberto ;
Rota, Rosella ;
Giordano, Antonio .
CELL CYCLE, 2009, 8 (01) :172-175
[10]   Deregulated expression of miR-21, miR-143 and miR-181a in non small cell lung cancer is related to clinicopathologic characteristics or patient prognosis [J].
Gao, Wen ;
Yu, Yue ;
Cao, Hailong ;
Shen, Hua ;
Li, Xiaodong ;
Pan, Shiyang ;
Shu, Yongqian .
BIOMEDICINE & PHARMACOTHERAPY, 2010, 64 (06) :399-408