Science et thérapie du cancer

miR-203 Functions as a Tumor Suppressor by Inhibiting Epithelial to Mesenchymal Transition in Ovarian Cancer

Abstract

Guannan Zhao, Yuqi Guo, Zixuan Chen, Yinan Wang, Chuanhe Yang, Andrew Dudas, Ziyun Du, Wen Liu, Yanan Zou, Erzsebet Szabo, Sue-Chin Lee, Michelle Sims, Weiwang Gu, Todd Tillmanns, Lawrence M. Pfeffer, Gabor Tigyi and Junming Yue

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 (slug) 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.