miR-203通过抑制卵巢癌上皮-间质转化发挥肿瘤抑制作用。
miR-203 Functions as a Tumor Suppressor by Inhibiting Epithelial to Mesenchymal Transition in Ovarian Cancer.
作者信息
Zhao Guannan, Guo Yuqi, Chen Zixuan, Wang Yinan, Yang Chuanhe, Dudas Andrew, Du Ziyun, Liu Wen, Zou Yanan, Szabo Erzsebet, Lee Sue-Chin, Sims Michelle, Gu Weiwang, Tillmanns Todd, Pfeffer Lawrence M, Tigyi Gabor, Yue Junming
机构信息
Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, USA; Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA; The Third Affiliated Hospital, Zhengzhou University, China.
The Third Affiliated Hospital, Zhengzhou University, China.
出版信息
J Cancer Sci Ther. 2015;7(2):34-43. doi: 10.4172/1948-5956.1000322.
OBJECTIVE
Ovarian cancer is a gynecological malignancy that has a high mortality rate in women due to metastatic progression and recurrence. miRNAs are small, endogenous, noncoding RNAs that function as tumor suppressors or oncogenes in various human cancers by selectively suppressing the expression of target genes. The objective of this study is to investigate the role of miR-203 in ovarian cancer.
METHODS
miR-203 was expressed in ovarian cancer SKOV3 and OVCAR3 cells using lentiviral vector and cell proliferation, migration, invasion were examined using MTT, transwell and Matrigel assays, respectively. Tumor growth was examined using Xenograft mouse model.
RESULTS
miR-203 expression was downregulated, whereas expression of its target gene Snai2 was upregulated in human ovarian serous carcinoma tissue as compared to normal ovaries. In addition, high miR-203 expression was associated with long-term survival rate of ovarian cancer patients. miR-203 overexpression inhibited cell proliferation, migration, and invasion of SKOV3 and OVCAR3 ovarian cancer cells. Furthermore, miR-203 overexpression inhibited the epithelial to mesenchymal transition (EMT) in ovarian cancer cells. Silencing Snai2 with lentiviral short hairpin (sh) RNA mimics miR-203-mediated inhibition of EMT and tumor cell invasion. Xenografts of miR-203-overexpressing ovarian cancer cells in immunodeficient mice exhibited a significantly reduced tumor growth.
CONCLUSION
miR-203 functions as a tumor suppressor by down regulating Snai2 in ovarian cancer.
目的
卵巢癌是一种妇科恶性肿瘤，因其转移进展和复发导致女性死亡率很高。微小RNA（miRNA）是小的内源性非编码RNA，通过选择性抑制靶基因的表达在多种人类癌症中发挥肿瘤抑制因子或癌基因的作用。本研究的目的是探讨miR-203在卵巢癌中的作用。
方法
使用慢病毒载体在卵巢癌SKOV3和OVCAR3细胞中表达miR-203，分别采用MTT法、Transwell法和基质胶实验检测细胞增殖、迁移和侵袭能力。使用异种移植小鼠模型检测肿瘤生长情况。
结果
与正常卵巢相比，人卵巢浆液性癌组织中miR-203表达下调，而其靶基因Snai2表达上调。此外，miR-203高表达与卵巢癌患者的长期生存率相关。miR-203过表达抑制SKOV3和OVCAR3卵巢癌细胞的增殖、迁移和侵袭。此外，miR-203过表达抑制卵巢癌细胞的上皮-间质转化（EMT）。用慢病毒短发夹（sh）RNA沉默Snai2可模拟miR-203介导的对EMT和肿瘤细胞侵袭的抑制作用。免疫缺陷小鼠中miR-203过表达的卵巢癌细胞异种移植瘤的生长明显减缓。
结论
miR-203在卵巢癌中通过下调Snai2发挥肿瘤抑制作用。
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