PMID- 31648104 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210110 IS - 2162-2531 (Print) IS - 2162-2531 (Electronic) IS - 2162-2531 (Linking) VI - 18 DP - 2019 Dec 6 TI - Blocking lncRNA MALAT1/miR-199a/ZHX1 Axis Inhibits Glioblastoma Proliferation and Progression. PG - 388-399 LID - S2162-2531(19)30250-1 [pii] LID - 10.1016/j.omtn.2019.09.005 [doi] AB - Zinc fingers and homeoboxes 1 (ZHX1) is a transcription repressor that has been implicated in the tumorigenesis and progression of diverse tumors. The functional role and regulating mechanism of ZHX1 has not been elucidated in glioblastoma (GBM). Previous reports have suggested that a large number of non-coding RNAs play a vital role in glioma initiation and progression. This study aimed to investigate the functional role and co-regulatory mechanisms of the metastasis-associated lung adenocarcinoma transcript-1 (MALAT1)/ microRNA-199a (miR-199a)/ZHX1 axis in GBM. We analyzed the expression of the MALAT1/miR-199a/ZHX1 axis and its correlation with patients' overall survival using two different glioma gene-expression datasets. A series of in vitro and in vivo studies including dual luciferase reporter assay, fluorescence in situ hybridization (FISH), RNA immunoprecipitation, and pull-down experiments were completed to elucidate the biological significance of the MALAT1/miR-199a/ZHX1 axis in promoting glioma proliferation and progression. Elevated ZHX1 expression correlated with poor prognosis in GBM patients, and in vitro studies demonstrated that ZHX1 attenuated GBM cell apoptosis by downregulation of pro-apoptotic protein (Bax) and upregulation of anti-apoptotic protein (Bcl-2). Furthermore, knockdown of MALAT1 inhibited GBM proliferation and progression in vitro and reduced tumor volume and prolonged survival in an orthotopic GBM murine model. Finally, we demonstrated that MALAT1 promoted ZHX1 expression via acting as a competing endogenous RNA by sponging miR-199a. The MALAT1/miR-199a/ZHX1 axis promotes GBM cell proliferation and progression in vitro and in vivo, and its expression negatively correlates with GBM patient survival. Blocking the MALAT1/miR-199a/ZHX1 axis can serve as a novel therapeutic strategy for treating GBM. CI - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Liao, Keman AU - Liao K AD - Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 160, Pujian Road, District Pudong, Shanghai 200127, China. FAU - Lin, Yingying AU - Lin Y AD - Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 160, Pujian Road, District Pudong, Shanghai 200127, China. FAU - Gao, Weizhen AU - Gao W AD - Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 160, Pujian Road, District Pudong, Shanghai 200127, China. FAU - Xiao, Zhipeng AU - Xiao Z AD - Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 160, Pujian Road, District Pudong, Shanghai 200127, China. FAU - Medina, Rogelio AU - Medina R AD - Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. FAU - Dmitriev, Pauline AU - Dmitriev P AD - Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. FAU - Cui, Jing AU - Cui J AD - Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. FAU - Zhuang, Zhengping AU - Zhuang Z AD - Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. FAU - Zhao, Xiaochun AU - Zhao X AD - Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, 350 W. Thomas Road, Phoenix, AZ 85013, USA. FAU - Qiu, Yongming AU - Qiu Y AD - Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 160, Pujian Road, District Pudong, Shanghai 200127, China. FAU - Zhang, Xiaohua AU - Zhang X AD - Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 160, Pujian Road, District Pudong, Shanghai 200127, China. Electronic address: 157223552@qq.com. FAU - Ge, Jianwei AU - Ge J AD - Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 160, Pujian Road, District Pudong, Shanghai 200127, China. FAU - Guo, Liemei AU - Guo L AD - Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 160, Pujian Road, District Pudong, Shanghai 200127, China. Electronic address: guolm001@126.com. LA - eng PT - Journal Article DEP - 20190917 PL - United States TA - Mol Ther Nucleic Acids JT - Molecular therapy. Nucleic acids JID - 101581621 PMC - PMC6819876 OTO - NOTNLM OT - MALAT1 OT - ZHX1 OT - competing endogenous RNA OT - glioblastoma OT - long non-coding RNA EDAT- 2019/10/28 06:00 MHDA- 2019/10/28 06:01 PMCR- 2019/09/17 CRDT- 2019/10/25 06:00 PHST- 2019/01/24 00:00 [received] PHST- 2019/08/18 00:00 [revised] PHST- 2019/09/10 00:00 [accepted] PHST- 2019/10/28 06:00 [pubmed] PHST- 2019/10/28 06:01 [medline] PHST- 2019/10/25 06:00 [entrez] PHST- 2019/09/17 00:00 [pmc-release] AID - S2162-2531(19)30250-1 [pii] AID - 10.1016/j.omtn.2019.09.005 [doi] PST - ppublish SO - Mol Ther Nucleic Acids. 2019 Dec 6;18:388-399. doi: 10.1016/j.omtn.2019.09.005. Epub 2019 Sep 17.