title: 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.
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.
authors.affiliation: Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Tan
authors.affiliation: Department of Radiotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Xinping
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Medical Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Qiangsheng
authors.initials: Q
authors.lastname: Dai
authors.affiliation: Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Biochemistry, University of Leicester, Leicester, UK.
authors.forename: Shiqiu
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yong yu
authors.initials: Yy
authors.lastname: Zhang
authors.affiliation: Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.|Department of Medical Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Heping
authors.initials: H
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis / Q000235:genetics; D019925:Cyclin A / Q000096:biosynthesis / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D000090683:Hippo Signaling Pathway; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009841:Oligonucleotides / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D014162:Transfection; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C526317:CCN2 protein, human; D019925:Cyclin A; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; C541915:Mirn129 microRNA, human; D009841:Oligonucleotides; D010750:Phosphoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D055513:Connective Tissue Growth Factor; D017346:Protein Serine-Threonine Kinases
keywords: TAZ; YAP; cell proliferation; miR-129-5p; survival