子宫内膜腺癌中EMT的发生及miR200a/ZEB1信号通路在该过程中发挥的作用

doi:10.6040/j.issn.1671-7554.0.2015.184

山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (7): 48-52.doi: 10.6040/j.issn.1671-7554.0.2015.184

子宫内膜腺癌中EMT的发生及miR200a/ZEB1信号通路在该过程中发挥的作用

张晓晖, 颜磊, 齐莎莎, 路真真, 李明江, 赵兴波

山东大学附属省立医院妇产科, 山东济南 250021

收稿日期:2015-02-13 修回日期:2015-04-22 出版日期:2015-07-10 发布日期:2015-07-10
通讯作者: 赵兴波。E-mail:zxb0626@126.com E-mail:zxb0626@126.com
基金资助:
国家自然科学基金(81272858, 81202507)

Occurrence of epithelia-mesenchymal transition in endometrial adenocarci-noma and the roles of miR200a/ZEB1 signaling pathway in this process

ZHANG Xiaohui, YAN Lei, QI Shasha, LU Zhenzhen, LI Mingjiang, ZHAO Xingbo

Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China

Received:2015-02-13 Revised:2015-04-22 Online:2015-07-10 Published:2015-07-10

摘要/Abstract

摘要： 目的检测上皮-间质转化(EMT)在子宫内膜腺癌中的发生, 并探讨miR200a/E盒结合锌指蛋白1(ZEB1)信号通路在其中发挥的作用。方法 ① 分组:取自石蜡切片的子宫内膜腺癌为A组(n=45), 正常子宫内膜为B组(n=22);取自手术中的子宫内膜腺癌标本为C组(n=34), 正常子宫内膜标本为D组(n=15);② 采用免疫组化法检测A、B两组间E钙黏蛋白(E-cadherin)、波形蛋白(Vimentin)、ZEB1的表达;采用Western blotting法检测C、D两组间上述3种蛋白的表达;③ Real-time RT-PCR法检测C、D两组间各蛋白相应mRNA及miR200a的表达。结果 ① B组与A组比较, E-cadherin表达降低(P<0.05), Vimentin及ZEB1表达升高(P<0.05);② D组与C组比较, E-cadherin蛋白及mRNA表达降低(P<0.05), Vimentin蛋白及mRNA表达升高(P<0.05), ZEB1蛋白及mRNA表达升高(P<0.05);③ 与C组数据相比, D组中miR200a表达量降低(P<0.05), D组中miR200a与E-cadherin的mRNA表达量之间存在正相关关系(r=0.63, P<0.01)。结论子宫内膜腺癌中明确发生了EMT过程, 而miR200a/ZEB1信号通路可对EMT过程中重要的分子标记物产生抑制作用。

关键词: 上皮-间质转化, 微小RNA200a, 调控作用, 子宫内膜腺癌, E盒结合锌指蛋白1

Abstract: Objective To investigate the occurrence of epithelia-mesenchymal transition (EMT) in endometrial carcinoma and examine the roles of miR200a/zinc finger E-box-binding protein 1(ZEB1) signaling pathway in this process. Methods Different groups of samples were collected, including paraffin sections of endometrial adenocarcinoma tissues (group A, n=22), endometrial tissues after resection of uterine myoma(group B, n=45), endometrial adenocarcinoma samples obtained during operation(group C, n=15) and healthy endometrial tissues(group D, n=34). Expressions of E-cadherin, Vimentin and ZEB1 in group A and group B were investigated with immunohistochemistry. Expressions of E-cadherin, Vimentin and ZEB1 and their mRNA in group C and group D were evaluated with Western blotting and Real-time RT-PCR. Expression of miR200a in group C and D was determined with Real-time RT-PCR. Results ① Compared with group A, group B had significantly decreased expression of E-cadherin, and markedly increased expressions of Vimentin and ZEB1(both P<0.05). ② Compared with group C, group D had decreased E-cadherin and its mRNA expressions but increased expressions of Vimentin and its mRNA, and ZEB1 and its mRNA (all P<0.05). ③ Compared with group C, group D exhibited remarkably elevated miR200a, which was positively correlated to E-cadherin's mRNA(r=0.63, P<0.01)as indicated by a linear regression analysis. Conclusions EMT occurs in endometrial adenocarcinoma. The miR200/ZEB1signaling pathway can inhibit the important molecular markers in EMT.

Key words: Epithelia-mesenchymal transition, Endometrial andenocarcinoma, Zinc finger E-box-binding protein 1, microRNA200a, Regulation

中图分类号:

R711.74

张晓晖, 颜磊, 齐莎莎, 路真真, 李明江, 赵兴波. 子宫内膜腺癌中EMT的发生及miR200a/ZEB1信号通路在该过程中发挥的作用[J]. 山东大学学报（医学版）, 2015, 53(7): 48-52.

ZHANG Xiaohui, YAN Lei, QI Shasha, LU Zhenzhen, LI Mingjiang, ZHAO Xingbo. Occurrence of epithelia-mesenchymal transition in endometrial adenocarci-noma and the roles of miR200a/ZEB1 signaling pathway in this process[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(7): 48-52.

参考文献

[1] Azueta A, Gatius S, Matias-Guiu X. Endometrioid carcinoma of the endometrium: pathologic and molecular features[J]. Semin Diagn Pathol, 2010, 27(4):226-240.
[2] Ombrato L, Malanchi I. The EMT universe: space between cancer cell dissemination and metastasis initiation[J]. Crit Rev Oncog, 2014, 19(5):349-361.
[3] Moyret-Lalle C, Ruiz E, Puisieux A. Epithelial-mesenchymal transition transcription factors and miRNAs: “plastic surgeons” of breast cancer[J]. World J Clin Oncol, 2014, 5(3):311-322.
[4] Zhu QC, Gao RY, Wu W, et al. Epithelial-mesenchymal transition and its role in the pathogenesis of colorectal cancer[J]. Asian Pac J Cancer Prev, 2013, 14(5):2689-2698.
[5] Vergara D, Merlot B, Lucot JP, et al. Epithelial-mesenchymal transition in ovarian cancer[J]. Cancer Lett, 2010, 291(1):59-66.
[6] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015[J]. CA Cancer J Clin, 2015, 65(1):5-29.
[7] Abal M, Llaurado M, Doll A, et al. Molecular determinants of invasion in endometrial cancer[J]. Clin Transl Oncol, 2007, 9(5):272-277.
[8] Giannoni E, Bianchini F, Masieri L, et al. Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness[J]. Cancer Res, 2010, 70(17):6945-6956.
[9] Vella LJ. The emerging role of exosomes in epithelial-mesenchymal-transition in cancer[J]. Front Oncol, 2014, 4:361.
[10] 洪伦. 上皮-间质转化及相关microRNA分子与肿瘤的恶性行为的研究进展[J]. 中国癌症杂志, 2011, 21(9):725-730. HONG Lun. EMT phenomenon and related microRNAs in the malignant progression of tumor[J]. China Oncology, 2011, 21(9):725-730.
[11] Heldin CH, Vanlandewijck M, Moustakas A. Regulation of EMT by TGFbeta in cancer[J]. FEBS Lett, 2012, 586(14):1959-1970.
[12] 刘苹, 李平, 彭艳, 等. 原代成纤维细胞和纤维肉瘤细胞自分泌转化生长因子β1浓度检测及对转化生长因子β1增殖的调节[J]. 中国组织工程研究与临床康复, 2011, 15(41):7669-7672. LIU Ping, LI Ping, PENG Yan, et al. Detection of autocrine transforming growth factor-beta β1 concentration in the primary fibroblasts and fibrosarcoma cells and effects on cell proliferation[J]. Journal of Clinical Rehabilitative Tissue Engineering Research, 2011, 15(41):7669-7672.
[13] Gregory PA, Bracken CP, Smith E, et al. An autocrine TGF-beta/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition[J]. Mol Biol Cell, 2011, 22(10):1686-1698.
[14] Garofalo M, Croce CM. Role of microRNAs in maintaining cancer stem cells[J]. Adv Drug Deliv Rev, 2015, 81:53-61. doi: 10.1016/j.addr.2014.11.014. Epub 2014 Nov 20.
[15] Korpal M, Kang Y. The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis[J]. RNA Biol, 2008, 5(3):115-119.
[16] Kinose Y, Sawada K, Nakamura K, et al. The role of microRNAs in ovarian cancer[J]. Biomed Res Int, 2014, 2014: 249393 . doi: 10.1155/2014/249393. Epub 2014 Sep 10.
[17] Li X, Roslan S, Johnstone CN, et al. MiR-200 can repress breast cancer metastasis through ZEB1-independent but moesin-dependent pathways[J]. Oncogene, 2014, 33(31):4077-4088.
[18] Chen Y, Xiao Y, Ge W, et al. miR-200b inhibits TGF-beta1-induced epithelial-mesenchymal transition and promotes growth of intestinal epithelial cells[J]. Cell Death Dis, 2013, 4:e541.doi: 10.1038/cddis.2013.22.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed

子宫内膜腺癌中EMT的发生及miR200a/ZEB1信号通路在该过程中发挥的作用

Occurrence of epithelia-mesenchymal transition in endometrial adenocarci-noma and the roles of miR200a/ZEB1 signaling pathway in this process

PDF (PC)

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 2

多维度评价

本文评价

推荐阅读 0

[1]	林雪艳,李春艳,侯小满,田永杰. PARP-1及EMT标志物在子宫腺肌病在位及异位内膜中的表达[J]. 山东大学学报（医学版）, 2017, 55(9): 36-40.
[2]	王平,陈静,史庆,傅艺冰. RbAp48在子宫内膜腺癌中的表达及临床意义[J]. 山东大学学报（医学版）, 2016, 54(5): 84-87.