Ascites promotes cell migration through the repression of miR-125b in ovarian cancer

// Lan Yang 1, * , Xiaoli Zhang 1, * , Yiming Ma 1 , Xinhua Zhao 1 , Bin Li 2 and Hongying Wang 1 1 State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China 2 Department of Gynecological Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China * Co-first authors Correspondence to: Hongying Wang, email: hongyingwang@cicams.ac.cn Bin Li, email: lb87960440@vip.sina.com Keywords: ovarian cancer, ascites, cell migration, TGF-β, miR-125b Received: January 05, 2017     Accepted: March 14, 2017     Published: April 05, 2017 ABSTRACT Interactions between ovarian cancer cells and the surrounding tumor microenvironment are not well characterized. Here, we investigated the molecular mechanisms by which malignant ascites promote the metastasis of ovarian cancer. It was found that ovarian cancer ascites promoted ovarian cancer cell migration which was attenuated by either heat inactivation or antibody blockade of TGF-β. High level (at ng/ml level) of TGF-β was detected in the ascites. In addition, ascites repressed the expression of miRNA-125b in a TGF-β-dependent manner. Mimic of miR-125b blocked ascites-induced cell migration. Furthermore, Gab2 (a target gene of miR-125b) was elevated by ascites in a TGF-β-dependent manner. And forced expression of Gab2 reversed the inhibition of migration induced by miR-125b mimic. Most importantly, the expression of miR-125b and Gab2 mRNA was negatively correlated in ovarian cancer specimens. Taken together, our finding suggested that TGF-β in ascites promoted cancer cell migration through repression of miR-125b in ovarian cancer. This might provide a novel therapeutic target for ovarian cancer in the future.