Blocking lncRNA MALAT1/miR-199a/ZHX1 Axis Inhibits Glioblastoma Proliferation and Progression
| Autor: | Pauline Dmitriev, Zhipeng Xiao, Xiaochun Zhao, Yingying Lin, Zhengping Zhuang, Weizhen Gao, Yongming Qiu, Jianwei Ge, Liemei Guo, Keman Liao, Xiaohua Zhang, Rogelio Medina, Jing Cui |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Biology medicine.disease_cause Article 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Glioma Drug Discovery medicine competing endogenous RNA MALAT1 Gene knockdown long non-coding RNA Competing endogenous RNA Cell growth lcsh:RM1-950 glioblastoma ZHX1 medicine.disease Long non-coding RNA lcsh:Therapeutics. Pharmacology 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Molecular Medicine Carcinogenesis |
| Zdroj: | Molecular Therapy. Nucleic Acids Molecular Therapy: Nucleic Acids, Vol 18, Iss, Pp 388-399 (2019) |
| ISSN: | 2162-2531 |
| Popis: | 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. Keywords: MALAT1, ZHX1, glioblastoma, competing endogenous RNA, long non-coding RNA |
| Databáze: | OpenAIRE |
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