Overexpressed miR-9 promotes tumor metastasis via targeting E-cadherin in serous ovarian cancer

• Published in: Frontiers of medicine 2017-06, Vol.11 (2), p.214-222
• Main Authors: Zhou, Bo, Xu, Hongbin, Xia, Meng, Sun, Chaoyang, Li, Na, Guo, Ensong, Guo, Lili, Shan, Wanying, Lu, Hao, Wu, Yifan, Li, Yuan, Yang, Degui, Weng, Danhui, Meng, Li, Hu, Junbo, Ma, Ding, Chen, Gang, Li, Kezhen
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Antigens, CD; Cadherins - genetics; Cadherins - metabolism; Carcinoma, Ovarian Epithelial; Cell adhesion & migration; Cell Line, Tumor; Cell Movement - genetics; E-cadherin; Epithelial-Mesenchymal Transition - genetics; Female; Gene Expression Regulation, Neoplastic; Humans; Medicine; Medicine & Public Health; Metastasis; MicroRNAs - genetics; MicroRNAs - metabolism; miR-9; Neoplasm Invasiveness - genetics; Neoplasm Metastasis - genetics; Neoplasms, Glandular and Epithelial - genetics; Neoplasms, Glandular and Epithelial - pathology; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Research Article; RNA, Messenger - genetics; Vimentin - metabolism
• ISSN: 2095-0217; 2095-0225
• DOI: 10.1007/s11684-017-0518-7

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.