title: CRNDE Promotes Malignant Progression of Glioma by Attenuating miR-384/PIWIL4/STAT3 Axis.
abstract: Colorectal neoplasia differentially expressed (CRNDE) is the most upregulated long noncoding RNA (lncRNA) in glioma. Herein, the function and potential molecular mechanisms of CRNDE and miR-384 were illustrated in glioma cells. CRNDE overexpression facilitated cell proliferation, migration, and invasion, while inhibited glioma cells apoptosis. Quantitative real-time polymerase chain reaction (PCR) demonstrated that miR-384 was downregulated in human glioma tissues and glioma cell lines. Moreover, restoration of miR-384 exerted tumor-suppressive functions. In addition, the expression of miR-384 was negatively correlated with CRNDE expression. A binding region between CRNDE and miR-384 was confirmed using luciferase assays. Moreover, CRNDE promoted cell malignant behavior by decreasing miR-384 expression. At the molecular level, treatment by CRNDE knockdown or miR-384 overexpression resulted in a decrease of piwi-like RNA-mediated gene silencing 4 (PIWIL4) protein. Besides, PIWIL4 was identified as a target of miR-384 and plays an oncogenic role in glioma. Similarly, downstream proteins of PIWIL4 such as STAT3, cyclin D1, VEGFA, SLUG, MMP-9, caspase 3, Bcl-2, and bcl-xL were modulated when treated with miR-384 and PIWIL4. Remarkably, CRNDE knockdown combined with miR-384 overexpression led to tumor regression in vivo. Overall, these results depicted a novel pathway mediated by CRNDE in glioma, which may be a potential application for glioma therapy.
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China; Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China; Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang, People's Republic of China.
authors.forename: Xiaobai
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People's Republic of China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China; Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang, People's Republic of China.
authors.forename: Chengbin
authors.initials: C
authors.lastname: Qu
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China; Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang, People's Republic of China. Electronic address: liuyh_cmuns@163.com.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D060565:Argonaute Proteins / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D064593:Heterografts; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D009857:Oncogenes; D011379:Prognosis; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D016601:RNA-Binding Proteins; D050796:STAT3 Transcription Factor / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; D060565:Argonaute Proteins; C586983:CRNDE RNA, human; C000619341:MIRN384 microRNA, human; D035683:MicroRNAs; C556795:PIWIL4 protein, human; D062085:RNA, Long Noncoding; D016601:RNA-Binding Proteins; D050796:STAT3 Transcription Factor