title: Long non-coding RNA CASC2 suppresses malignancy in human gliomas by miR-21.
abstract: Long non-coding RNAs (lncRNAs) are aberrantly expressed in many diseases including cancer. LncRNA CASC2 (cancer susceptibility candidate 2) has been characterized as a tumor suppressor in endometrial cancer and colorectal cancer. However, the role and function of CASC2 in human gliomas remain unknown. In this study, we confirmed that CASC2 was lowly expressed in glioma tissues as well as in U251 and U87 glioma cell lines. Overexpression of CASC2 inhibited the malignancy of glioma cells, including proliferation, migration, and invasion, and promoted cell apoptosis. MicroRNA-21 (miR-21) has been reported to be overexpressed in human glioma tissues and cell lines, which is responsible for the malignant progression of glioma. We found that up-regulated CASC2 decreased the expression of miR-21 significantly and there is a reciprocal repression between CASC2 and miR-21 in an Argonaute2-dependent manner. Furthermore, bioinformatics, luciferase reporter assays and pull-down assay confirmed that miR-21 binds to CASC2 in a sequence-specific manner. Introduction of miR-21 largely abrogated CASC2-mediated inhibition of glioma cell proliferation, migration, and invasion, and promotion of cell apoptosis. This study demonstrated that CASC2 plays a tumor suppressive role in glioma via negative regulation of miR-21, which may be a novel therapeutic target for treating gliomas.
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China.
authors.forename: Zhi-Qing
authors.initials: ZQ
authors.lastname: Li
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China. Electronic address: xueyixue888@163.com.
authors.forename: Yi-Xue
authors.initials: YX
authors.lastname: Xue
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D060565:Argonaute Proteins / Q000378:metabolism; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D005910:Glioma / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000378:metabolism*; D016415:Sequence Alignment; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C466422:AGO2 protein, human; D060565:Argonaute Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D025521:Tumor Suppressor Proteins; C484713:long non-coding RNA CASC2, human
keywords: CASC2; Glioma; Invasion; MiR-21; Migration; Proliferation