胃癌中DNA甲基化对miR-200c 141表达影响的研究

周欣亮; 张璁; 王玉栋; 赵连梅; 桑梅香; 单保恩

doi:10.3969/j.issn.1000-8179.2017.02.119

胃癌中DNA甲基化对miR-200c 141表达影响的研究

doi: 10.3969/j.issn.1000-8179.2017.02.119

周欣亮^①,,
张璁^②,
王玉栋^①,
赵连梅^②,
桑梅香^②,
单保恩^{②, ③, ,}

①.
河北医科大学第四医院肿瘤内科（石家庄市 050011）
②.
科研中心（石家庄市 050011）
③.
河北省肿瘤研究所（石家庄市 050011）

详细信息

作者简介:
周欣亮，专业方向为肿瘤的精准治疗及非编码RNA在肿瘤中的作用机制等基础研究。E-mail：zhouxlhappy@hotmail.com

通讯作者:
单保恩，baoenshan1962@126.com

计量
- 文章访问数: 75
- HTML全文浏览量: 1
- PDF下载量: 2
- 被引次数: 0
出版历程
- 收稿日期: 2016-09-23
- 修回日期: 2017-01-12
- 刊出日期: 2017-01-30

MiR-200c/141 methylation inhibits the expression of miR-200c and miR-141 in gastric cancer

ZHOU Xinliang^{①
,},
ZHANG Cong^②,
WANG Yudong^①,
ZHAO Lianmei^②,
SANG Meixiang^②,
SHAN Baoen^{②, ③
, ,}

①.
Oncology Department, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
②.
Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
③.
Tumor Research Institute of Hebei, Shijiazhuang 050011, China

More Information

Corresponding author: Baoen SHAN; E-mail:baoenshan1962@126.com

摘要

摘要: 目的探讨胃癌组织中miR-200c/141CpG岛的甲基化水平与miR-200c/141表达水平和临床病理特征的相关性。方法运用实时定量PCR（qRT-PCR）和BS-MSP方法检测胃癌组织和癌旁组织中miR-200c/141CpG岛的表达与其基因甲基化水平。统计学分析miR-200c/141CpG岛的甲基化水平与miR-200c/141水平和临床病理特征的关系。结果 miR-200c/141CpG岛的甲基化水平在胃癌组织中显著升高，miR-200c和miR-141的水平显著降低，miR-200c/141CpG岛的甲基化水平与miR-200c和miR-141的水平呈负相关。结论胃癌组织中升高的miR-200c/141CpG岛的甲基化水平诱导miR-200c和miR-141表达降低。
- 胃癌 /
- 甲基化 /
- miR-200c /
- miR-141 /
- 临床病理特征
Abstract: Objective This work aims to detect the levels of miR-200c/141 methylation and miR-200c/141 in gastric cancer tissue and investigate the relationship between miR-200c/141 expression and clinical parameters. Methods The methylation status of miR-200c/ 141 CpG island and miR-200c/141 in gastric cancer tissue specimens was evaluated by qRT-PCR or BS-MSP method. We analyzed the relationship among the methylation status of miR-200c/141 CpG island, expression level of miR-200c or miR-141, and clinical parameters. Results The status of miR-200c/141 CpG island methylation in gastric cancer tissue was significantly higher compared with that in paracarcinoma tissue. MiR-200c and miR-141 were markedly decreased in gastric cancer tissue compared with those in adjacent tissue. MiR-200c/141 CpG island methylation was negatively related with the expression of miR-200c and miR-141 in gastric cancer specimens. Conclusion The upregulation of miR-200c/141 CpG methylation inhibits miR-200c/141 expression in gastric cancer tissue.
- gastric cancer /
- methylation /
- miR-200c /
- miR-141 /
- clinicopathological feature

HTML全文

图 1 miR-200c/141CpG岛在DNA中所处的位置

Figure 1. Locations of the hypermethylated fragment of miR-200c/141. One CpG island located at 500 bp upstream of the miR-200c/141 genomic sequence

下载: 全尺寸图片幻灯片

图 2 miR-200c和miR-141在胃癌中的表达情况

Figure 2. Differential expression of miR-200c and miR-141 in gastric cancer specimens

A. miR-200c expression in gastric cancer tissue and paired adjacent tissue; B. miR-141 expression in gastric cancer tissue and paired adjacent tissue. Results were normalized to values for the paired adjacent tissue

下载: 全尺寸图片幻灯片

图 3 胃癌标本中miR-200c/141上游CpG岛的甲基化水平

Figure 3. Methylation status of miR-200c/141 CpG island was analyzed by bisulfite conversion-and methylation-specific PCR in gastric cancer tissue and adjacent tissue

A. The methylation and demethylation of miR-200c/141 CpG island were showed by Gel Imaging; B. Methylation status of miR-200c/141 CpG island was showed by histogram. Results were normalized to results for the paired adjacent tissue

下载: 全尺寸图片幻灯片

表 1 胃癌中miR-200c/141CPG岛甲基化水平与胃癌患者临床病理特征的关系

Table 1. Correlations of the methylation status of miR-200c/141 CpG island in gastric cancer specimens with the clinicopathological feature

表 2 miR-200c/141上游CpG岛的甲基化水平与miR-200c和miR-141表达的相关性

Table 2. Correlations of the expression levels of miR-200c and miR-141 in gastric cancer specimens with the expression level of TGF-β and CpG island cytosine methylation level of miR-200c/141

参考文献(16)

[1]	Standart N, Jackson RJ. MicroRNAs repress translation of m7Gpppcapped target mRNAs in vitro by inhibiting initiation and promoting deadenylation[J]. Genes Dev, 2007, 21(16):1975-1982. doi: 10.1101/gad.1591507
[2]	Nilsen TW. Mechanisms of microRNA-mediated gene regulation in animal cells[J]. Trends Genet, 2007, 23(5):243-249. doi: 10.1016/j.tig.2007.02.011
[3]	Damiano V, Brisotto G, Borgna S, et al. Epigenetic silencing of miR-200c in breast cancer is associated with aggressiveness and is modulated by ZEB1[J]. Genes Chromosomes Cancer, 2016.[Epub ahead of print]. doi: 10.1002/gcc.22422/abstract
[4]	Vrba L, Jensen TJ, Garbe JC, et al. Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells[J]. PLoS One, 2010, 5(1):e8697. doi: 10.1371/journal.pone.0008697
[5]	Paterson EL, Kazenwadel J, Bert AG, et al. Down-regulation of the miRNA-200 family at the invasive front of colorectal cancers with degraded basement membrane indicates EMT is involved in cancer progression[J]. Neoplasia, 2013, 15(2):180-191. doi: 10.1593/neo.121828
[6]	Liu S, Tetzlaff MT, Wang T, et al. miR-200c/Bmi1 axis and epithelialmesenchymal transition contribute to acquired resistance to BRAF inhibitor treatment[J]. Pigment Cell Melanoma Res, 2015, 28(4):431-441. doi: 10.1111/pcmr.12379
[7]	Abedi N, Mohammadi-Yeganeh S, Koochaki A, et al. miR-141 as potential suppressor of β-catenin in breast cancer[J]. Tumour Biol, 2015, 36(12):9895-9901. doi: 10.1007/s13277-015-3738-y
[8]	Wu PP, Zhu HY, Sun XF, et al. MicroRNA-141 regulates the tumour suppressor DLC1 in colorectal cancer[J]. Neoplasma, 2015, 62(5):705-712. doi: 10.4149/neo_2015_084
[9]	Zhou H, Tang K, Xiao H, et al. A panel of eight-miRNA signature as a potential biomarker for predicting survival in bladder cancer[J]. J Exp Clin Cancer Res, 2015, 34(1):53. doi: 10.1186/s13046-015-0167-0
[10]	Chen X, Wang X, Ruan A, et al. miR-141 is a key regulator of renal cell carcinoma proliferation and metastasis by controlling EphA2 expression[J]. Clin Cancer Res, 2014, 20(10):2617-2630. doi: 10.1158/1078-0432.CCR-13-3224
[11]	Calin GA, Sevignani C, Dumitru CD, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers[J]. Proc Natl Acad Sci U S A, 2004, 101(9):2999-3004. doi: 10.1073/pnas.0307323101
[12]	Makunin IV, Pheasant M, Simons C, et al. Orthologous microRNA genes are located in cancer-associated genomic regions in human and mouse[J]. PLoS One, 2007, 2(11):ell33. http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.283.7001
[13]	Lujambio A, Esteller M. CpG island hypermethylation of tumor suppressor microRNAs in human cancer[J]. Cell Cycle, 2007, 6(12):1455-1459. http://www.citeulike.org/user/capitall/article/1409489
[14]	Wu A, Wu K, Li M, et al. Upregulation of microRNA-492 induced by epigenetic drug treatment inhibits the malignant phenotype of clear cell renal cell carcinoma in vitro[J]. Mol Med Rep, 2015, 12(1): 1413-1420. https://www.researchgate.net/publication/274258609_Upregulation_of_microRNA-492_induced_by_epigenetic_drug_treatment_inhibits_the_malignant_phenotype_of_clear_cell_renal_cell_carcinoma_in_vitro
[15]	Yang Y, Huang JQ, Zhang X, et al. MiR-129-2 functions as a tumor suppressor in glioma cells by targeting HMGB1 and is down-regulated by DNA methylation[J]. Mol Cell Biochem, 2015, 404(1-2):229-239. doi: 10.1007/s11010-015-2382-6
[16]	Guo W, Zhu TN, Dong ZM, et al. Aberrant methylation and expression of growth arrest and DNA-damage-inducible 45G gene inesophageal squamous-cell carcinoma[J]. TUMOR, 2013, 33(1):74-80. https://www.researchgate.net/publication/289042249_Aberrant_methylation_and_expression_of_growth_arrest_and_DNA-damage-inducible_45G_gene_in_esophageal_squamous-cell_carcinoma