title: Upregulation of miR-130b enhances stem cell-like phenotype in glioblastoma by inactivating the Hippo signaling pathway.
abstract: The Hippo signaling pathway plays a crucial role in suppressing tumorigenesis. Physiologically, The Hippo signaling largely restricts its two downstream effectors, homologous oncoproteins Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), to a low level of activity by the MST1-SAV1 complex-induced kinase cascade. However, how the negative regulation induced by MST1-SAV1 complex is disrupted to exhibit constitutive YAP/TAZ activation in cancer remains unclear. Herein, we reported that miR-130b directly repressed MST1 and SAV1 expression in human glioblastoma cells. Overexpression of miR-130b induced hyperactivation of the YAP/TAZ and enhanced expression of the Hippo signaling downstream genes CTGF and the pluripotency associated markers, including CD133, SOX2, Nanog, MYC and BMI1, leading to promotion of glioblastoma stem cell phenotype. Conversely, inhibition of miR-130b attenuated these effects. These findings provide a novel mechanism for Hippo signaling inactivation in cancer, indicating not only a potentially pivotal role for miR-130b in the progression of glioblastoma, but also may represent a new therapeutic target.
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Zhujiang Hospital of South Medical University, Guangzhou, Guangdong, 510280, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, China.
authors.forename: Maimaitili
authors.initials: M
authors.lastname: Mijiti
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, China.
authors.forename: Zengliang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, China. Electronic address: dangmurenjiafu@sina.com.
authors.forename: Dangmuren
authors.initials: D
authors.lastname: Jiafu
mesh_terms: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D005838:Genotype; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000090683:Hippo Signaling Pathway; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008156:Luciferases; D035683:MicroRNAs; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C554019:MIRN130 microRNA, human; C415864:SAV1 protein, human; C088374:YAP1 protein, human; C108675:TAFAZZIN protein, human; C095566:STK4 protein, human; D000099317:Hippo Kinases
keywords: Cancer stem cell; Glioblastoma; Hippo signaling; miR-130b