Characterization of human gastric carcinoma-related methylation of 9 miR CpG islands and repression of their expressions in vitro and in vivo

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• 作者：Yantao Du (1)
  Zhaojun Liu (1)
  Liankun Gu (1)
  Jing Zhou (1)
  Bu-dong Zhu (2)
  Jiafu Ji (3)
  Dajun Deng (1)
  
• 刊名：BMC Cancer
• 出版年：2012
• 出版时间：December 2012
• 年：2012
• 卷：12
• 期：1
• 全文大小：994KB
• 参考文献：1. Hu X, Macdonald DM, Huettner PC, Feng Z, El Naqa IM, Schwarz JK, Mutch DG, Grigsby PW, Powell SN, Wang X: A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer. / Gynecol Oncol 2009,114(3):457-64. CrossRef
  2. Lu Y, Ryan SL, Elliott DJ, Bignell GR, Futreal PA, Ellison DW, Bailey S, Clifford SC: Amplification and overexpression of Hsa-miR-30b, Hsa-miR-30d and KHDRBS3 at 8q24.22-q24.23 in medulloblastoma. / PLoS One 2009,4(7):e6159. CrossRef
  3. Slaby O, Svoboda M, Fabian P, Smerdova T, Knoflickova D, Bednarikova M, Nenutil R, Vyzula R: Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. / Oncology 2007,72(5-):397-02. CrossRef
  4. Markou A, Tsaroucha EG, Kaklamanis L, Fotinou M, Georgoulias V, Lianidou ES: Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR. / Clin Chem 2008,54(10):1696-704. CrossRef
  5. Corthals SL, Jongen-Lavrencic M, de Knegt Y, Peeters JK, Beverloo HB, Lokhorst HM, Sonneveld P: Micro-RNA-15a and micro-RNA-16 expression and chromosome 13 deletions in multiple myeloma. / Leuk Res 2010,34(5):677-81. CrossRef
  6. Dijkstra MK, van Lom K, Tielemans D, Elstrodt F, Langerak AW, van ’t Veer MB, Jongen-Lavrencic M: 17p13/TP53 deletion in B-CLL patients is associated with microRNA-34a downregulation. / Leukemia 2009,23(3):625-27. CrossRef
  7. Murchison EP, Partridge JF, Tam OH, Cheloufi S, Hannon GJ: Characterization of Dicer-deficient murine embryonic stem cells. / Proc Natl Acad Sci U S A 2005,102(34):12135-2140. CrossRef
  8. Tie J, Pan Y, Zhao L, Wu K, Liu J, Sun S, Guo X, Wang B, Gang Y, Zhang Y, / et al.: MiR-218 inhibits invasion and metastasis of gastric cancer by targeting the Robo1 receptor. / PLoS Genet 2010,6(3):e1000879. CrossRef
  9. Laneve P, Gioia U, Andriotto A, Moretti F, Bozzoni I, Caffarelli E: A minicircuitry involving REST and CREB controls miR-9- expression during human neuronal differentiation. / Nucleic Acids Res 2010,38(20):6895-905. CrossRef
  10. Lu L, Katsaros D, de la Longrais IA, Sochirca O, Yu H: Hypermethylation of let-7a-3 in epithelial ovarian cancer is associated with low insulin-like growth factor-II expression and favorable prognosis. / Cancer Res 2007,67(21):10117-0122. CrossRef
  11. Lodygin D, Tarasov V, Epanchintsev A, Berking C, Knyazeva T, K?rner H, Knyazev P, Diebold J, Hermeking H: Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. / Cell Cycle 2008,7(16):2591-600. CrossRef
  12. Furuta M, Kozaki KI, Tanaka S, Arii S, Imoto I, Inazawa J: miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. / Carcinogenesis 2010,31(5):766-76. CrossRef
  13. Tsuruta T, Kozaki K, Uesugi A, Furuta M, Hirasawa A, Imoto I, Susumu N, Aoki D, Inazawa J: miR-152 is a tumor suppressor microRNA that is silenced by DNA hypermethylation in endometrial cancer. / Cancer Res 2011,71(20):6450-462. CrossRef
  14. Tsai KW, Wu CW, Hu LY, Li SC, Liao YL, Lai CH, Kao HW, Fang WL, Huang KH, Chan WC, / et al.: Epigenetic regulation of miR-34b and miR-129 expression in gastric cancer. / Int J Cancer 2011,129(11):2600-610. CrossRef
  15. Hildebrandt MA, Gu J, Lin J, Ye Y, Tan W, Tamboli P, Wood CG, Wu X: Hsa-miR-9 methylation status is associated with cancer development and metastatic recurrence in patients with clear cell renal cell carcinoma. / Oncogene 2010,29(42):5724-728. CrossRef
  16. Hashimoto Y, Akiyama Y, Otsubo T, Shimada S, Yuasa Y: Involvement of epigenetically silenced microRNA-181c in gastric carcinogenesis. / Carcinogenesis 2010,31(5):777-84. CrossRef
  17. Yang C, Cai J, Wang Q, Tang H, Cao J, Wu L, Wang Z: Epigenetic silencing of miR-130b in ovarian cancer promotes the development of multidrug resistance by targeting colony-stimulating factor 1. / Gynecol Oncol 2012,124(2):325-34. CrossRef
  18. Deng D, Liu Z, Du Y: Epigenetic alterations as cancer diagnostic, prognostic, and predictive biomarkers. / Adv Genet 2010, 71:125-76. CrossRef
  19. Lehmann U, Hasemeier B, Christgen M, Müller M, R?mermann D, L?nger F, Kreipe H: Epigenetic inactivation of microRNA gene hsa-mir-9- in human breast cancer. / J Pathol 2008,214(1):17-4. CrossRef
  20. Bandres E, Agirre X, Bitarte N, Ramirez N, Zarate R, Roman-Gomez J, Prosper F, Garcia-Foncillas J: Epigenetic regulation of microRNA expression in colorectal cancer. / Int J Cancer 2009,125(11):2737-743. CrossRef
  21. Chen X, Hu H, Guan X, Xiong G, Wang Y, Wang K, Li J, Xu X, Yang K, Bai Y: CpG island methylation status of miRNAs in esophageal squamous cell carcinoma. / Int J Cancer 2012,130(7):17-4.
  22. Kozaki K, Imoto I, Mogi S, Omura K, Inazawa J: Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. / Cancer Res 2008,68(7):2094-105. CrossRef
  23. Balaguer F, Link A, Lozano JJ, Cuatrecasas M, Nagasaka T, Boland CR, Goel A: Epigenetic silencing of miR-137 is an early event in colorectal carcinogenesis. / Cancer Res 2010,70(16):6609-618. CrossRef
  24. Chen Q, Chen X, Zhang M, Fan Q, Luo S, Cao X: miR-137 is frequently down-regulated in gastric cancer and is a negative regulator of Cdc42. / Dig Dis Sci 2011,56(7):2009-016. CrossRef
  25. Li X, Lin R, Li J: Epigenetic silencing of microRNA-375 regulates PDK1 expression in esophageal cancer. / Dig Dis Sci 2011,56(10):2849-856. CrossRef
  26. Suzuki H, Yamamoto E, Nojima M, Kai M, Yamano HO, Yoshikawa K, Kimura T, Kudo T, Harada E, Sugai T, / et al.: Methylation-associated silencing of microRNA-34b/c in gastric cancer and its involvement in an epigenetic field defect. / Carcinogenesis 2010,31(12):2066-073. CrossRef
  27. Tanaka N, Toyooka S, Soh J, Kubo T, Yamamoto H, Maki Y, Muraoka T, Shien K, Furukawa M, Ueno T, / et al.: Frequent methylation and oncogenic role of microRNA-34b/c in small-cell lung cancer. / Lung Cancer 2012,76(1):32-8. CrossRef
  28. Liu Z, Shen J, Zhang L, Shen L, Li Q, Zhang B, Zhou J, Gu L, Feng G, Ma J, / et al.: Prevalence of A2143G mutation of H. pylori-23S rRNA in Chinese subjects with and without clarithromycin use history. / BMC Microbiol 2008, 8:81. CrossRef
  29. Danesh J, Lewington S, Thompson SG, Lowe GD, Collins R, Kostis JB, Wilson AC, Folsom AR, Wu K, Benderly M, / et al.: Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. / JAMA 2005,294(14):1799-809. CrossRef
  30. Eads CA, Laird PW: Combined bisulfite restriction analysis (COBRA). / Methods Mol Biol 2002, 200:71-5.
  31. Deng DJ, Deng GR, Smith MF, Zhou J, Xin HJ, Powell SM, Lu YY: Simultaneous detection of CpG methylation and single nucleotide polymorphism by denaturing high performance liquid chromatography. / Nucleic Acids Res 2002,30(3):13E. CrossRef
  32. Bahrami AR, Dickman MJ, Matin MM, Ashby JR, Brown PE, Conroy MJ, Fowler GJ, Rose JP, Sheikh QI, Yeung AT, / et al.: Use of fluorescent DNA-intercalating dyes in the analysis of DNA via ion-pair reversed-phase denaturing high-performance liquid chromatography. / Anal Biochem 2002,309(2):248-52. CrossRef
  33. Luo D, Zhang B, Lv L, Xiang S, Liu Y, Ji J, Deng D: Methylation of CpG islands of p16 associated with progression of primary gastric carcinomas. / Lab Invest 2006,86(6):591-98.
  34. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, / et al.: MicroRNA expression profiles classify human cancers. / Nature 2005,435(7043):834-38. CrossRef
  35. Zheng Z, Li L, Liu X, Wang D, Tu B, Wang L, Wang H, Zhu WG: 5-Aza-2'-deoxycytidine reactivates gene expression via degradation of pRb pocket proteins. / FASEB J 2011,26(1):449-59. CrossRef
  36. Tellez CS, Juri DE, Do K, Bernauer AM, Thomas CL, Damiani LA, Tessema M, Leng S, Belinsky SA: EMT and stem cell-like properties associated with miR-205 and miR-200 epigenetic silencing are early manifestations during carcinogen-induced transformation of human lung epithelial cells. / Cancer Res 2011,71(8):3087-097. CrossRef
  37. Rauhala HE, Jalava SE, Isotalo J, Bracken H, Lehmusvaara S, Tammela TL, Oja H, Visakorpi T: miR-193b is an epigenetically regulated putative tumor suppressor in prostate cancer. / Int J Cancer 2010,127(6):1363-372. CrossRef
  38. Chim CS, Wong KY, Leung CY, Chung LP, Hui PK, Chan SY, Yu L: Epigenetic inactivation of the hsa-miR-203 in haematological malignancies. / J Cell Mol Med 2011,15(12):2760-767. CrossRef
  39. Tsukamoto Y, Nakada C, Noguchi T, Tanigawa M, Nguyen LT, Uchida T, Hijiya N, Matsuura K, Fujioka T, Seto M, / et al.: MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14--3zeta. / Cancer Res 2010,70(6):2339-349. CrossRef
  40. Tsai KW, Liao YL, Wu CW, Hu LY, Li SC, Chan WC, Ho MR, Lai CH, Kao HW, Fang WL, / et al.: Aberrant hypermethylation of miR-9 genes in gastric cancer. / Epigenetics 2011,6(10):1189-197. CrossRef
  41. Díaz R, Silva J, García JM, Lorenzo Y, García V, Pe?a C, Rodríguez R, Mu?oz C, García F, Bonilla F, / et al.: Deregulated expression of miR-106a predicts survival in human colon cancer patients. / Genes Chromosomes Cancer 2008,47(9):794-02. CrossRef
  42. Isik M, Korswagen HC, Berezikov E: Expression patterns of intronic microRNAs in Caenorhabditis elegans. / Silence 2010,1(1):5. CrossRef
  43. Sikand K, Slane SD, Shukla GC: Intrinsic expression of host genes and intronic miRNAs in prostate carcinoma cells. / Cancer Cell Int 2009, 9:21. CrossRef
  44. Wilting SM, van Boerdonk RA, Henken FE, Meijer CJ, Diosdado B, Meijer GA, le Sage C, Agami R, Snijders PJ, Steenbergen RD: Methylation-mediated silencing and tumour suppressive function of hsa-miR-124 in cervical cancer. / Mol Cancer 2010, 9:167. CrossRef
  45. Delaloy C, Liu L, Lee JA, Su H, Shen F, Yang GY, Young WL, Ivey KN, Gao FB: MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell-derived neural progenitors. / Cell Stem Cell 2010,6(4):323-35. CrossRef
  46. Liu S, Kumar SM, Lu H, Liu A, Yang R, Pushparajan A, Guo W, Xu X: MicroRNA-9 up-regulates E-cadherin through inhibition of NF-κB1-Snail1 pathway in melanoma. / J Pathol 2012,226(1):61-2. CrossRef
  47. Deng Y, Deng H, Bi F, Liu J, Bemis LT, Norris D, Wang XJ, Zhang Q: MicroRNA-137 targets carboxyl-terminal binding protein 1 in melanoma cell lines. / Int J Biol Sci 2011,7(1):133-37. CrossRef
  48. Langevin SM, Stone RA, Bunker CH, Grandis JR, Sobol RW, Taioli E: MicroRNA-137 promoter methylation in oral rinses from patients with squamous cell carcinoma of the head and neck is associated with gender and body mass index. / Carcinogenesis 2010,31(5):864-70. CrossRef
  49. Langevin SM, Stone RA, Bunker CH, Lyons-Weiler MA, Laframboise WA, Kelly L, Seethala RR, Grandis JR, Sobol RW, Taioli E: MicroRNA-137 promoter methylation is associated with poorer overall survival in patients with squamous cell carcinoma of the head and neck. / Cancer 2011,117(7):1454-462. CrossRef
  50. Corney DC, Flesken-Nikitin A, Godwin AK, Wang W, Nikitin AY: MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. / Cancer Res 2007,67(18):8433-438. CrossRef
  51. Cho WC: Epigenetic alteration of microRNAs in feces of colorectal cancer and its clinical significance. / Expert Rev Mol Diagn 2011,11(7):691-94. CrossRef
  52. Kubo T, Toyooka S, Tsukuda K, Sakaguchi M, Fukazawa T, Soh J, Asano H, Ueno T, Muraoka T, Yamamoto H, / et al.: Epigenetic silencing of microRNA-34b/c plays an important role in the pathogenesis of malignant pleural mesothelioma. / Clin Cancer Res 2011,17(15):4965-974. CrossRef
  53. Watanabe K, Emoto N, Hamano E, Sunohara M, Kawakami M, Kage H, Kitano K, Nakajima J, Goto A, Fukayama M, / et al.: Genome structure-based screening identified epigenetically silenced microRNA associated with invasiveness in non-small-cell lung cancer. / Int J Cancer 2012,130(11):2580-590. CrossRef
  54. Mazar J, Khaitan D, DeBlasio D, Zhong C, Govindarajan SS, Kopanathi S, Zhang S, Ray A, Perera RJ: Epigenetic regulation of microRNA genes and the role of miR-34b in cell invasion and motility in human melanoma. / PLoS One 2011,6(9):e24922. CrossRef
  55. Suzuki H, Yamamoto E, Nojima M, Kai M, Yamano HO, Yoshikawa K, Kimura T, Kudo T, Harada E, Sugai T, / et al.: Methylation-associated silencing of microRNA-34b/c in gastric cancer and its involvement in an epigenetic field defect. / Carcinogenesis 2010,31(12):2066-073. CrossRef
  56. Adam L, Zhong M, Choi W, Qi W, Nicoloso M, Arora A, Calin G, Wang H, Siefker-Radtke A, McConkey D, / et al.: miR-200 expression regulates epithelial-to-mesenchymal transition in bladder cancer cells and reverses resistance to epidermal growth factor receptor therapy. / Clin Cancer Res 2009,15(16):5060-072. CrossRef
  57. Bracken CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J, Shannon MF, Goodall GJ: A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. / Cancer Res 2008,68(19):7846-854. CrossRef
  58. Davalos V, Moutinho C, Villanueva A, Boque R, Silva P, Carneiro F, Esteller M: Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis. / Oncogene 2012,31(16):2062-074. CrossRef
  59. Li A, Omura N, Hong SM, Vincent A, Walter K, Griffith M, Borges M, Goggins M: Pancreatic cancers epigenetically silence SIP1 and hypomethylate and overexpress miR-200a/200b in association with elevated circulating miR-200a and miR-200b levels. / Cancer Res 2010,70(13):5226-237. CrossRef
  60. Ying Q, Liang L, Guo W, Zha R, Tian Q, Huang S, Yao J, Ding J, Bao M, Ge C, / et al.: Hypoxia-inducible microRNA-210 augments the metastatic potential of tumor cells by targeting vacuole membrane protein 1 in hepatocellular carcinoma. / Hepatology 2011,54(6):2064-075. CrossRef
  61. Tsuchiya S, Fujiwara T, Sato F, Shimada Y, Tanaka E, Sakai Y, Shimizu K, Tsujimoto G: MicroRNA-210 regulates cancer cell proliferation through targeting fibroblast growth factor receptor-like 1 (FGFRL1). / J Biol Chem 2011,286(1):420-28. CrossRef
  62. Lages E, Guttin A, El Atifi M, Ramus C, Ipas H, Dupré I, Rolland D, Salon C, Godfraind C, de Fraipont F, / et al.: MicroRNA and target protein patterns reveal physiopathological features of glioma subtypes. / PLoS One 2011,6(5):e20600. CrossRef
  63. de Souza Rocha Simonini P, Breiling A, Gupta N, Malekpour M, Youns M, Omranipour R, Malekpour F, Volinia S, Croce CM, Najmabadi H, / et al.: Epigenetically deregulated microRNA-375 is involved in a positive feedback loop with estrogen receptor alpha in breast cancer cells. / Cancer Res 2010,70(22):9175-184. CrossRef
  64. Mazar J, DeBlasio D, Govindarajan SS, Zhang S, Perera RJ: Epigenetic regulation of microRNA-375 and its role in melanoma development in humans. / FEBS Lett 2011,585(15):2467-476. CrossRef
  65. Craig VJ, Cogliatti SB, Rehrauer H, Wündisch T, Müller A: Epigenetic silencing of microRNA-203 dysregulates ABL1 expression and drives Helicobacter-associated gastric lymphomagenesis. / Cancer Res 2011,71(10):3616-624. CrossRef
  66. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/12/249/prepub
  
• 作者单位：Yantao Du (1)
  Zhaojun Liu (1)
  Liankun Gu (1)
  Jing Zhou (1)
  Bu-dong Zhu (2)
  Jiafu Ji (3)
  Dajun Deng (1)
  
  1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Cancer Etiology, Peking University Cancer Hospital and Institute, Fu-Cheng-Lu, No.52, Haidian District, Beijing, 100142, China
  2. Department of Oncology, Peking University Cancer Hospital and Institute, Fu-Cheng-Lu, No.52, Haidian District, Beijing, 100142, China
  3. Department of Surgery, Peking University Cancer Hospital and Institute, Fu-Cheng-Lu, No.52, Haidian District, Beijing, 100142, China
  
• ISSN：1471-2407

文摘

Background Many miR genes are located within or around CpG islands. It is unclear whether methylation of these CpG islands represses miR transcription regularly. The aims of this study are to characterize gastric carcinoma (GC)-related methylation of miR CpG islands and its relationship with miRNA expression. Methods Methylation status of 9 representative miR CpG islands in a panel of cell lines and human gastric samples (including 13 normal biopsies, 38 gastritis biopsies, 112 pairs of GCs and their surgical margin samples) was analyzed by bisulfite-DHPLC and sequencing. Mature miRNA levels were determined with quantitative RT-PCR. Relationships between miR methylation, transcription, GC development, and clinicopathological characteristics were statistically analyzed. Results Methylation frequency of 5 miR CpG islands (miR-9-1, miR-9-3, miR-137, miR-34b, and miR-210) gradually increased while the proportion of methylated miR-200b gradually decreased during gastric carcinogenesis (Ps-lt;-.01). More miR-9-1 methylation was detected in 62%-64% of the GC samples and 4% of the normal or gastritis samples (18/28 versus 2/48; Odds ratio, 41.4; P-lt;-.01). miR-210 methylation showed high correlation with H. pylori infection. miR-375, miR-203, and miR-193b methylation might be host adaptation to the development of GCs. Methylation of these miR CpG islands was consistently shown to significantly decrease the corresponding miRNA levels presented in human cell lines. The inverse relationship was also observed for miR-9-1, miR-9-3, miR-137, and miR-200b in gastric samples. Among 112 GC patients, miR-9-1 methylation was an independent favourable predictor of overall survival of GC patients in both univariate and multivariate analysis (P-lt;-.02). Conclusions In conclusion, alteration of methylation status of 6 of 9 tested miR CpG islands was characterized in gastric carcinogenesis. miR-210 methylation correlated with H. pylori infection. miR-9-1 methylation may be a GC-specific event. Methylation of miR CpG islands may significantly down-regulate their transcription regularly.