A novel role for microRNA-129-5p in inhibiting ovarian cancer cell proliferation and survival via direct suppression of transcriptional co-activators YAP and TAZ

// Guosheng Tan 1, * , Xinping Cao 2, * , Qiangsheng Dai 3, * , Bing Zhang 4 , Jianwen Huang 5 , Shiqiu Xiong 6 , Yong yu Zhang 1 , Wei Chen 1 , Jianyong Yang 1 , Heping Li 1, 3 1 Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 2 Department of Radiotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China 3 Department of Medical Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 4 Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 5 Department of Radiation Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 6 Department of Biochemistry, University of Leicester, Leicester, UK * These authors have contributed equally to this work Correspondence to: Heping Li, e-mail: drliheping@163.com Jianyong Yang, e-mail: yangjy1959@163.com Keywords: miR-129-5p, YAP, TAZ, cell proliferation, survival Received: November 30, 2014 Accepted: January 28, 2015 Published: April 07, 2015 ABSTRACT Transcriptional co-activator Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are key oncogenes in mammalian cells. Activities of YAP and TAZ are largely restricted by the Hippo tumor suppressor pathway through phosphorylation-ubiquitination mechanisms. The involvement of microRNA in cancer progression has recently been reported, though whether they have a role in activating YAP and TAZ in human cancer cells remains unclear. Here, we report a microRNA, miR-129-5p, directly represses YAP and TAZ expression, leading to the inactivation of TEA domain (TEAD) transcription, and the downregulation of Hippo downstream genes, connective tissue growth factor (CTGF) and Cyclin A. Furthermore, we reveal miR-129-5p inhibits ovarian cancer cell proliferation, survival and tumorigenicity, and that downregulation of miR-129-5p in ovarian cancer cells highly correlates with malignant progression and poor survival. Hence, we demonstrate a novel mechanism for YAP and TAZ activation in cancers, indicating not only a potentially pivotal role for miR-129-5p in the progression of ovarian cancer, but also offering new therapeutic strategies to circumvent the disease.