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Overexpressed miR-9 promotes tumor metastasis via targeting E-cadherin in serous ovarian cancer |
Bo Zhou1,2, Hongbin Xu3, Meng Xia1, Chaoyang Sun1, Na Li1, Ensong Guo1, Lili Guo1, Wanying Shan1, Hao Lu1, Yifan Wu1, Yuan Li1, Degui Yang3, Danhui Weng1, Li Meng1, Junbo Hu1, Ding Ma1, Gang Chen1, Kezhen Li1() |
1. Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 2. Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan 430071, China 3. Department of Gynecology and Obstetrics, the People’s Hospital of Shenzhen, Shenzhen 518000, China |
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Abstract MicroRNAs (miRNAs) play critical roles in the development and progression in various cancers. Dysfunctional miR-9 expression remains ambiguous, and no consensus on the metastatic progression of ovarian cancer has been reached. In this study, results from the bioinformatics analysis show that the 3′-UTR of the E-cadherin mRNA was directly regulated by miR-9. Luciferase reporter assay results confirmed that miR-9 could directly target this 3′-UTR. miR-9 and E-cadherin expression in ovarian cancer tissue was quantified by qRT-PCR. Migration and invasion were detected by wound healing and Transwell system assay in SKOV3 and A2780. qRT-PCR and Western blot were performed to detect the epithelial?mesenchymal transition-associated mRNA and proteins. Immunofluorescence technique was used to analyze the expression and subcellular localization of E-cadherin, N-cadherin, and vimentin. The results showed that miR-9 was frequently upregulated in metastatic serous ovarian cancer tissue compared with paired primary ones. Upregulation of miR-9 could downregulate the expression of E-cadherin but upregulate the expression of mesenchymal markers (N-cadherin and vimentin). Overexpression of miR-9 could promote the cell migration and invasion in ovarian cancer, and these processes could be effectively inhibited via miR-9 inhibitor. Thus, our study demonstrates that miR-9 may promote ovarian cancer metastasis via targeting E-cadherin and a novel potential therapeutic approach to control metastasis of ovarian cancer.
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Keywords
ovarian cancer
metastasis
miR-9
E-cadherin
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Corresponding Author(s):
Kezhen Li
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Online First Date: 04 May 2017
Issue Date: 01 June 2017
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