• 南京醫(yī)科大學附屬淮安第一醫(yī)院普外科(江蘇淮安 223300);

目的  探討甲狀腺乳頭狀癌(PTC)中微小RNA-34b(miR-34b)基因的表達及其啟動子區(qū)的甲基化情況,并分析甲基化與其臨床病理特征的關(guān)系。
方法  收集2008年9月至2010年10月期間南京醫(yī)科大學附屬淮安第一醫(yī)院行手術(shù)切除的25例PTC患者的癌組織和癌旁組織。采用實時定量PCR法檢測其miR-34bmRNA的表達,采用甲基化特異性(MSP)PCR法檢測miR-34b基因啟動子區(qū)的甲基化情況。
結(jié)果  PTC癌組織中miR-34bmRNA的相對表達量為0.85±0.05,較癌旁組織的1.62±0.09低(P=0.030)。25例PTC癌組織中,有18例(72%)患者的miR-34b基因啟動子區(qū)發(fā)生甲基化,癌旁組織組有10例(40%),癌組織的甲基化比例較高(P=0.021)。甲基化與PTC患者的年齡、性別、腫瘤大小、TNM分期和包膜浸潤均無關(guān)(P>0.05),而與淋巴結(jié)轉(zhuǎn)移有關(guān),發(fā)生淋巴結(jié)轉(zhuǎn)移者的甲基化比例高于未發(fā)生淋巴結(jié)轉(zhuǎn)移者(P<0.05)。
結(jié)論  PTC癌組織中miR-34b基因啟動子區(qū)的異常甲基化可能是該基因失活的原因之一,并且可能與PTC的發(fā)生、發(fā)展以及轉(zhuǎn)移均有關(guān),其機理值得進一步研究。

引用本文: 韓學東,任毅,甄林林. miR-34b基因啟動子區(qū)甲基化與甲狀腺乳頭狀癌的關(guān)系△. 中國普外基礎(chǔ)與臨床雜志, 2013, 20(6): 627-631. doi: 復(fù)制

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14. Xing M, Cohen Y, Mambo E, et al. Early occurrence of RASSF1Ahypermethylation and its mutual exclusion with BRAF mutation inthyroid tumorigenesis[J]. Cancer Res, 2004, 64(5):1664-1668.
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18. Mathé E, Nguyen GH, Funamizu N, et al. Inflammation regulates microRNA expression in cooperation with p53 and nitric oxide[J]. Int J Cancer, 2012, 131(3):760-765.
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20. Benassi B, Flavin R, Marchionni L, et al. MYC is activated by USP2a-mediated modulation of microRNAs in prostate cancer[J]. Cancer Discov, 2012, 2(3):236-247.
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23. Tsai KW, Wu CW, Hu LY, et al. Epigenetic regulation of miR-34b and miR-129 expression in gastric cancer[J]. Int J Cancer, 2011, 129(11):2600-2610.
24. Balça-Silva J, Sousa Neves S, Gonçalves AC, et al. Effect of miR-34b overexpression on the radiosensitivity of non-small cell lung cancer cell lines[J]. Anticancer Res, 2012, 32(5):1603-1609.
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26. , 23(5):1117-1124.
27. , 3(1):83-92.
  1. 1. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002[J]. JAMA, 2006, 295(18):2164-2167.
  2. 2. How J, Tabah R. Explaining the increasing incidence of differentiated thyroid cancer[J]. CMAJ, 2007, 177(11):1383-1384.
  3. 3. Yip L, Kelly L, Shuai Y, et al. MicroRNA signature distinguishes the degree of aggressiveness of papillary thyroid carcinoma[J]. Ann Surg Oncol, 2011, 18(7):2035-2041.
  4. 4. Yanaihara N, Caplen N, Bowman E, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis[J]. Cancer Cell, 2006, 9(3):189-198.
  5. 5. 姚汝鋮, 鄭軍, 邢榮春. 微小RNA在胰腺癌中的研究進展[J]. 中國普外基礎(chǔ)與臨床雜志, 2012, 19(8):911-915.
  6. 6. Lopez-Serra P, Esteller M. DNA methylation-associated silencingof tumor-suppressor microRNAs in cancer[J]. Oncogene, 2012, 31(13):1609-1622.
  7. 7. Mackiewicz M, Huppi K, Pitt JJ, et al. Identification of the receptor tyrosine kinase AXL in breast cancer as a target for the human miR-34a microRNA[J]. Breast Cancer Res Treat, 2011, 130(2):663-679.
  8. 8. Nalls D, Tang SN, Rodova M, et al. Targeting epigenetic regulation of miR-34a for treatment of pancreatic cancer by inhibition of pancreatic cancer stem cells[J]. PLoS One, 2011, 6(8):e24099.
  9. 9. Gao LB, Li LJ, Pan XM, et al. A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer[J]. Biol Chem, 2013, 394(3):415-420.
  10. 10. Vogt M, Munding J, Grüner M, et al. Frequent concomitant inactivation of miR-34a and miR-34b/c by CpG methylation in colorectal, pancreatic, mammary, ovarian, urothelial, and renal cell carcinomas and soft tissue sarcomas[J]. Virchows Arch, 2011, 458(3):313-322.
  11. 11. Hoque MO, Rosenbaum E, Westra WH, et al. Quantitative assessment of promoter methylation profiles in thyroid neoplasms[J]. J Clin Endocfinol Metab, 2005, 90(7):4011-4018.
  12. 12. Hiroki E, Suzuki F, Akahira J, et al. MicroRNA-34b functions as a potential tumor suppressor in endometrial serous adenocarcinoma[J]. Int J Cancer, 2012, 131(4):E395-E404.
  13. 13. Wong KY, Yu L, Chim CS. DNA methylation of tumor suppressormiRNA genes:a lesson from the miR-34 family[J]. Epigenomics,.
  14. 14. Xing M, Cohen Y, Mambo E, et al. Early occurrence of RASSF1Ahypermethylation and its mutual exclusion with BRAF mutation inthyroid tumorigenesis[J]. Cancer Res, 2004, 64(5):1664-1668.
  15. 15. Ogasawara S, Maesawa C, Yamamoto M, et al. Disruption ofcell-type-specific methylation at the maspin gene promoter is frequ-ently involved in undifferentiated thyroid cancers[J]. Oncogene,.
  16. 16. He L, He X, Lim LP, et al. A microRNA component of the p53 tumour suppressor network[J]. Nature, 2007, 447(7148):1130-1134.
  17. 17. 張明, 劉衛(wèi)輝, 尤楠, 等. 7種microRNAs在原發(fā)性肝癌組織和癌旁組織間的差異表達及與血清腫瘤標志物水平的相關(guān)性研究[J]. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(6):562-566.
  18. 18. Mathé E, Nguyen GH, Funamizu N, et al. Inflammation regulates microRNA expression in cooperation with p53 and nitric oxide[J]. Int J Cancer, 2012, 131(3):760-765.
  19. 19. Yamazaki H, Chijiwa T, Inoue Y, et al. Overexpression of the miR-34 family suppresses invasive growth of malignant melanomawith the wild-type p53 gene[J]. Exp Ther Med, 2012, 3(5):793-796.
  20. 20. Benassi B, Flavin R, Marchionni L, et al. MYC is activated by USP2a-mediated modulation of microRNAs in prostate cancer[J]. Cancer Discov, 2012, 2(3):236-247.
  21. 21. Majid S, Dar AA, Saini S, et al. miRNA-34b inhibits prostate cancer through demethylation, active chromatin modifications, and AKT pathways[J]. Clin Cancer Res, 2013, 19(1):73-84.
  22. 22. Du Y, Liu Z, Gu L, et al. Characterization of human gastric carcinoma-related methylation of 9 miR CpG islands and repression of their expressions in vitro and in vivo[J]. BMC Cancer, 2012, 12:249.
  23. 23. Tsai KW, Wu CW, Hu LY, et al. Epigenetic regulation of miR-34b and miR-129 expression in gastric cancer[J]. Int J Cancer, 2011, 129(11):2600-2610.
  24. 24. Balça-Silva J, Sousa Neves S, Gonçalves AC, et al. Effect of miR-34b overexpression on the radiosensitivity of non-small cell lung cancer cell lines[J]. Anticancer Res, 2012, 32(5):1603-1609.
  25. 25. Wang Z, Chen Z, Gao Y, et al. DNA hypermethylation of microRNA-34b/c has prognostic value for stage Ⅰ non-small cell lung cancer[J]. Cancer Biol Ther, 2011, 11(5):490-496.
  26. 26. , 23(5):1117-1124.
  27. 27. , 3(1):83-92.
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