期刊论文详细信息
Journal of Translational Medicine
Mir-655 up-regulation suppresses cell invasion by targeting pituitary tumor-transforming gene-1 in esophageal squamous cell carcinoma
Guoqiang Zhao2  Ziming Dong2  Tao Wang4  Xudong Chen1  Ping Li3  Min Li2  Yunyun Ma2  Yuwen Du2  Wenqiao Zang2  Yuanyuan Wang2 
[1] Department of Histology and Embryology, Luohe Medical College, Luohe, Henan 462002, China;College of Basic Medical Sciences, Zhengzhou University, No.100 Kexue Road, Zhengzhou, Henan 450001, China;Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China;Department of Hemato-tumor, The First Affiliated Hospital of Henan University of TCM, Zhengzhou, Henan 450000, China
关键词: PTTG1;    Invasion;    miR-655;    Esophageal squamous cell carcinoma;   
Others  :  824359
DOI  :  10.1186/1479-5876-11-301
 received in 2013-11-11, accepted in 2013-12-03,  发布年份 2013
PDF
【 摘 要 】

Background

MicroRNAs (miRNAs) can act as either oncogenes or tumor suppressor genes under different conditions and thus can play a significant role in cancer development. We investigated miR-655 expression in a cohort of esophageal squamous cell carcinoma (ESCC) to assess the impact of this miRNA on ESCC cell invasion and metastasis.

Methods

A qRT-PCR assay was used to quantify miR-655 expression levels in 34 paired ESCC samples and adjacent non-tumor tissues. Wound healing and transwell assays were used to evaluate the effects of miR-655 expression on the invasiveness of ESCC cells. Luciferase reporter and western blot assays were used to determine whether the mRNA encoding pituitary tumor-transforming gene-1 (PTTG1) is a major target of miR-655.

Results

The expression level of miR-655 in ESCC tissues was found to be lower than in adjacent non-tumor tissues (P < 0.05). This relatively low expression level was significantly associated with the occurrence of lymph node metastases (P < 0.05). Migration rates were significantly lower for two ESCC-derived cell lines (EC9706 and KYSE150) transfected with miR-429 mimics (P < 0.05). Subsequent western blot and luciferase reporter assays demonstrated that miR-655 could bind to putative binding sites within the PTTG1 mRNA 3’-untranslated region (3’-UTR) and thus reduce the expression.

Conclusions

miR-655 is expressed at low levels in primary ESCC tissues, and up-regulation of miR-655 inhibits ESCC cell invasiveness by targeting PTTG1. Our findings suggest that PTTG1 may act as a major target of miR-655. This study improves our understanding of the mechanisms underlying ESCC pathogenesis and may promote the development of novel targeted therapies.

【 授权许可】

   
2013 Wang et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140713031524686.pdf 2630KB PDF download
Figure 6. 59KB Image download
Figure 5. 40KB Image download
Figure 4. 70KB Image download
Figure 3. 63KB Image download
Figure 2. 39KB Image download
Figure 1. 36KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】
  • [1]Ambros V: The functions of animal microRNAs. Nature 2004, 431(7006):350-355.
  • [2]Kim VN, Nam JW: Genomics of microRNA. Trends Genet 2006, 22(3):165-173.
  • [3]Kwak PB, Iwasaki S, Tomari Y: The microRNA pathway and cancer. Cancer Sci 2010, 101(11):2309-2315.
  • [4]Farazi TA, Spitzer JI, Morozov P, Tuschl T: miRNAs in human cancer. J Pathol 2011, 223(2):102-115.
  • [5]Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116(2):281-297.
  • [6]Zamore PD, Haley B: Ribo-gnome: the big world of small RNAs. Science 2005, 309(5740):1519-1524.
  • [7]Brennecke J, Cohen SM: Towards a complete description of the microRNA complement of animal genomes. Genome Biol 2003, 4(9):228. BioMed Central Full Text
  • [8]Chan JA, Krichevsky AM, Kosik KS: MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 2005, 65(14):6029-6033.
  • [9]Jensen RH, Tiirikainen M, You L, Ginzinger D, He B, Uematsu K, Xu Z, Treseler P, McCormick F, Jablons DM: Genomic alterations in human mesothelioma including high resolution mapping of common regions of DNA loss in chromosome arm 6q. Anticancer Res 2003, 23(3B):2281-2289.
  • [10]Lee RC, Feinbaum RL, Ambros V: The C elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993, 75(5):843-854.
  • [11]Wightman B, Ha I, Ruvkun G: Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 1993, 75(5):855-862.
  • [12]He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, Calin GA, Liu CG, Franssila K, Suster S, Kloos RT, Croce CM, de la Chapelle A: The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci 2005, 102(52):19075-19080.
  • [13]Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, Yuen ST, Chan TL, Kwong DL, Au GK, Liu CG, Calin GA, Croce CM, Harris CC: MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 2008, 299(4):425-436.
  • [14]Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 2006, 9(3):189-198.
  • [15]Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Ménard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM: MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005, 65(16):7065-7070.
  • [16]Iorio MV, Visone R, Di LG, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, Calin GA, Ménard S, Croce CM: MicroRNA signatures in human ovarian cancer. Cancer Res 2007, 67(18):8699-8707.
  • [17]Lewis BP, Burge CB, Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005, 120(1):15-20.
  • [18]Harazono Y, Muramatsu T, Endo H, Uzawa N, Kawano T, Harada K, Inazawa J: miR-655 Is an EMT-Suppressive MicroRNA Targeting ZEB1 and TGFBR2. PLoS ONE 2013, 8(5):e62757.
  • [19]Pei L, Melmed S: Isolation and characterization of a pituitary tumor-transforming gene (PTTG). Mol Endocrinol 1997, 11:433-441.
  • [20]Bradshaw C, Kakar SS: Pituitary tumor transforming gene: an important gene in normal cellular functions and tumorigenesis. Histol Histopathol 2007, 22:219-226.
  • [21]Boelaert K, McCabe CJ, Tannahill LA, Gittoes NJL, Holder RL, Watkinson JC, Bradwell AR, Sheppard MC, Franklyn JA: Pituitary tumor transforming gene and fibroblast growth factor-2 expression: potential prognostic indicators in differentiated thyroid cancer. J Clin Endocrinol Metab 2003, 88:2341-2347.
  • [22]Ramaswamy S, Ross KN, Lander ES, Golub TR: A molecular signature of metastasis in primary solid tumors. Nat Genet 2003, 33:49-54.
  • [23]Pavet V, Portal MM, Moulin JC, Herbrecht R, Gronemeyer H: Towards novel paradigms for cancer therapy. Oncogene 2011, 30:1-20.
  • [24]Yoon CH, Kim MJ, Lee H, Kim RK, Lim EJ, Yoo KC, Lee GH, Cui YH, Oh YS, Gye MC, Lee YY, Park IC, An S, Hwang SG, Park MJ, Suh Y, Lee SJ: PTTG1 oncogene promotes tumor malignancy via epithelial to mesenchymal transition and expansion of cancer stem cell population. J Biol Chem 2012, 287:19516-19527.
  • [25]Salehi F: Kovacs1 K, Scheithauer BW, Lloyd RV, Cusimano M: pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update. Endocr Relat Cancer 2008, 15:721-743.
  • [26]Shibata Y, Haruki N, Kuwabara Y, et al.: Expression of PTTG (pituitary tumor transforming gene) in esophageal squamous cell cancer. Jpn J Clin Oncol 2002, 32:233-237.
  • [27]Solbach C, Roller M, Fellbaum C, Nicoletti M, Kaufmann M: PTTG mRNA expression in primary breast cancer: a prognostic marker for lymph node invasion and tumor recurrence. Breast 2004, 13:80-81.
  • [28]Schickel R, Boyerinas B, Park SM, Peter ME: MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene 2008, 27(45):5959-5974.
  • [29]Gao Y, Chen Z, Zhang L, Zhou F, Shi S, Feng X, Li B, Meng X, Ma X, Luo M, Shao K, Li N, Qiu B, Mitchelson K, Cheng J, He J: Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma. Cancer Res 2008, 68(1):26-33.
  • [30]Calin GA, Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer 2006, 6(11):857-866.
  • [31]Farazi TA, Hoell JI: Pavel Morozov, and Thomas Tuschl: microRNAs in human cancer. Adv Exp Med Biol 2013, 774:1-20.
  • [32]Zhang X, Horwitz GA, Prezant TR, Valentini A, Nakashima M, Bronstein MD, Melmed S: Structure, expression, and function of human pituitary tumor-transforming gene (PTTG). Mol Endocrinol 1999, 13:156-66.
  • [33]Hamid T, Kakar SS: PTTG and cancer. Histol Histopathol 2003, 18:245-51.
  • [34]Wen CY, Nakayama T, Wang AP, et al.: Expression of pituitary tumor transforming gene in human gastric carcinoma. World J Gastroenterol 2004, 10:481-483.
  • [35]Chambers AF, Matrisian LM: Changing view of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst 1997, 89:1260-1270.
  • [36]Basset P, Okada A, Chenard MP, Kannan R, Stoll I, Anglard P, Bellocq JP, Rio MC: Matrix metalloproteinases as stromal effectors of human carcinoma progression therapeutical implications. Matrix Biol 1997, 15:535-541.
  • [37]Johnsen M, Lund LR, Romer J, Almholt K, Dano K: Cancer invasion and tissues remodeling: common themes in proteolytic matrix degradation. Curr Opin Cell Biol 1998, 10:667-671.
  • [38]Shima I, Sasaguri Y, Kusukawa J, Yamana H, Fujita H, Kakegawa T, Morimatsu M: Production of matrix metalloproteinase-2 and metalloproteinase-3 related to malignant behavior of esophageal squamous cell carcinoma. A clinicopathologic study. Cancer 1992, 70:2747-2753.
  • [39]Ohashi K, Nemoto T, Nakamura K, Nemori R: Increased expression of matrix metalloproteinase 7 and 9 and membrane type 1-matrix metalloproteinase in esophageal squamous cell carcinomas. Cancer 2000, 88:2201-2209.
  • [40]Hongli L, Chonggao Y, Baogang Z, Yonghong S, Lihong S, Ningbo L, Shujuan L, Shijun L, Yuqing L, Jin Z, Fengjie L, Wentong L, Fei L, Lei S, Yueliang Q: PTTG1 Promotes Migration and Invasion of Human Non-small Cell Lung Cancer Cells and is modulated by miR-186. Carcinogenesis 2013. May 13
  文献评价指标  
  下载次数:16次 浏览次数:12次