Relationship Between Methylation of MiR-34b Gene Promoter and Papillary Thyroid Carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HAN Xuedong , REN Yi ,  ZHEN Linlin

Department of General Surgery， Huai’an First People’s Hospital， Nanjing Medical University， Huai’an 223300， Jiangsu Province， China;

Corresponding author：

ZHEN Linlin, Email: simu1027@sina.com

Keywords：

Micro RNA-34b; Methylation; Papillary thyroid carcinoma; DNA

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Objective 　To investigate the expression level and methylation level of micro RNA-34b（miR-34b） gene in papillary thyroid carcinoma （PTC）， and to analyze the relationship between methylation and clinicopathological characters of PTC.
Methods 　PTC tissues and tumor adjacent tissues were collected from 25 patients with PTC who underwent operation in Huai’an First People’s Hospital of Nanjing Medical University from Sep. 2008 to Oct. 2010. Expression of miR-34b gene and level of methylation in gene promoter were detected by real time PCR and methylation-specific PCR in the 2 kinds of tissues， respectively.
Results 　The expression value of miR-34b mRNA in PTC tissues was 0.85±0.05， which was significantly lower than those of tumor adjacent tissues （1.62±0.09）， P=0.030. There were methylation in 18 （72%，18/25） PTC tissues， and 10 （40%，10/25） in tumor adjacent tissues， and the ratio of methylation was higher in PTC tissues （P=0.021）. In PTC tissues， methylation was not related to age， gender， tumor size， TNM stage， and invasion of the capsule （P＞0.05）， but was related to lymph node metastasis （P＜0.05）. Ratio of methylation in patients with lymph node metastasis was significantly higher than those of patients with no lymph node metastasis.
Conclusion 　Methylation of miR-34b gene promoter is one of the reasons for inactivation of PTC， and it may be related to the development and metastasis of PTC， which needs to be further investigated.

Citation： HAN Xuedong,REN Yi,ZHEN Linlin. Relationship Between Methylation of MiR-34b Gene Promoter and Papillary Thyroid Carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(6): 627-631. doi: Copy

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27.	， 3(1)：83-92.

1. Davies L， Welch HG. Increasing incidence of thyroid cancer in the United States， 1973-2002[J]. JAMA， 2006， 295(18)：2164-2167.
2. How J， Tabah R. Explaining the increasing incidence of differentiated thyroid cancer[J]. CMAJ， 2007， 177(11)：1383-1384.
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. 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. 姚汝铖，郑军，邢荣春. 微小RNA在胰腺癌中的研究进展[J]. 中国普外基础与临床杂志， 2012， 19(8)：911-915.
6. Lopez-Serra P， Esteller M. DNA methylation-associated silencingof tumor-suppressor microRNAs in cancer[J]. Oncogene， 2012， 31(13)：1609-1622.
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. 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. 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. 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. 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. 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. Wong KY， Yu L， Chim CS. DNA methylation of tumor suppressormiRNA genes：a lesson from the miR-34 family[J]. Epigenomics，.
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. 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. 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. 张明，刘卫辉，尤楠，等. 7种microRNAs在原发性肝癌组织和癌旁组织间的差异表达及与血清肿瘤标志物水平的相关性研究[J]. 中国普外基础与临床杂志， 2010， 17(6)：562-566.
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. 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. 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. 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. 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. 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.
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. ， 23(5)：1117-1124.
27. ， 3(1)：83-92.

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Relationship Between Methylation of MiR-34b Gene Promoter and Papillary Thyroid Carcinoma

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