title: MicroRNA-144 suppresses tumorigenesis and tumor progression of astrocytoma by targeting EZH2.
abstract: Our previous study demonstrated that enhancer of zeste homolog 2 (EZH2) overexpression may be associated with aggressive tumor progression and poor prognosis in human astrocytoma. The aim of this study was to investigate the underlying mechanisms of EZH2 on astrocytoma tumorigenesis. An online program miRWalk (http://www.umm.uni-heidelberg.de/apps/zmf/mirwalk/) was used to predict possible microRNAs (miRNAs) that might target EZH2 messenger RNA (mRNA). Then the functions of the miRNA-EZH2 mRNA axis in astrocytoma cell proliferation, invasion, and migration were also assessed. We further evaluated the clinical value of the miRNA-EZH2 mRNA axis in astrocytomas. As a result, we identified EZH2 as a target gene of miR-144. In addition, forced expression of miR-144 suppressed astrocytoma cell proliferation, invasion, and migration by down-regulating EZH2. Moreover, miR-144 down-regulation and EZH2 mRNA up-regulation were both significantly associated with advanced World Health Organization grades and low Karnofsky performance status score of astrocytoma patients. Importantly, survival analysis identified the combined expression of miR-144 and EZH2 (miR-144/EZH2) as an independent prognostic factor for overall survival in astrocytoma patients. In conclusion, miR-144 may function as a tumor suppressor by regulating EZH2 expression, and miR-144/EZH2 expression may be a highly sensitive marker for the prognosis in astrocytoma patients.
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Medical College, Shantou University, Shantou 515041, China.
authors.forename: Lvbiao
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Medical College, Shantou University, Shantou 515041, China.
authors.forename: Yungui
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Experimental Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.
authors.forename: Yanyang
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Department of Experimental Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Experimental Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Medical College, Shantou University, Shantou 515041, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Medical College, Shantou University, Shantou 515041, China.
authors.forename: Liepeng
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Medical College, Shantou University, Shantou 515041, China. Electronic address: yjunst@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
mesh_terms: D000328:Adult; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D016016:Proportional Hazards Models; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome
chemical_list: C554293:MIRN144 microRNA, human; D035683:MicroRNAs; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
keywords: Astrocytoma; Clinicopathological feature; Enhancer of zeste homolog 2; MicroRNA-144; Prognosis; Tumorigenesis