LncRNA IDH1-AS1 suppresses cell proliferation and tumor growth in glioma

• Published in: Biochemistry and cell biology Vol. 98; no. 5; pp. 556 - 564
• Main Authors: Wang, Jubo, Quan, Yu, Lv, Jian, Dong, Quan, Gong, Shouping
• Format: Journal Article
• Language: English
• Published: 1840 Woodward Drive, Suite 1, Ottawa, ON K2C 0P7 NRC Research Press 01.09.2020; Canadian Science Publishing NRC Research Press
• Subjects: Aged; Animals; Apoptosis; Brain cancer; brain neoplasm; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain tumors; Caspase-3; Caspase-9; Cell cycle; Cell growth; Cell Proliferation; Cell viability; Cyclin-dependent kinase 2; Cyclin-dependent kinase 4; Enzymatic activity; Enzymes; Expressed sequence tags; Female; G1 phase; Genetic aspects; Glioblastoma; glioblastome; Glioma; Glioma - metabolism; Glioma - pathology; Glioma cells; Gliomas; Growth; Humans; IDH1; IDH1 protein; Isocitrate dehydrogenase; lncRNA IDH1-AS1; long ARNnc IDH1-AS1; Male; Mice; Mice, Nude; Middle Aged; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; néoplasie cérébrale; prolifération cellulaire; Protein expression; Proteins; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Tumor Cells, Cultured; Tumorigenesis; Tumors; China; glioblastoma; cell proliferation; IDH1; lncRNA IDH1-AS1; brain neoplasm; néoplasie cérébrale; long ARNnc IDH1-AS1; prolifération cellulaire; glioblastome
• ISSN: 0829-8211; 1208-6002
• DOI: 10.1139/bcb-2019-0465

Glioma is a type of brain tumor that is common globally, and is associated with a variety of genetic changes. It has been reported that isocitrate dehydrogenase 1 (IDH1) is overexpressed in glioma and in HeLa cells. The lncRNA IDH1-AS1 is believed to interact with IDH1, and when IDH1-AS1 is overexpressed, HeLa cell proliferation is inhibited. However, the effects of IDH1-AS1 on glioma were relatively unknown. The results from this work show that IDH1-AS1 is downregulated in the glioma tissues. We used primary glioblastoma cell lines U251 and U87-MG to study the effects of IDH1-AS1 on glioma cell growth, in vitro and in vivo. We found that when IDH1-AS1 is overexpressed cell proliferation is inhibited, cell cycle is arrested at the G1 phase, and the protein expression levels of cyclinD1, cyclinA, cyclinE, CDK2, and CDK4 are decreased. We found that cell apoptosis was increased when IDH1-AS1 was overexpressed, as evidenced by increases in the levels of cleaved caspase-9 and -3. Conversely, knockdown of IDH1-AS1 promoted cell proliferation. Moreover, we proved that overexpression of IDH1-AS1 inhibits the tumorigenesis of U251 cells, in vivo. Furthermore, IDH1-AS1 did not affect IDH1 protein expression, but altered its enzymatic activities in glioma cells. Silencing of IDH1 reversed the effects of IDH1-AS1 upregulation on cell viability. Hence, our study provides first-hand evidence for the effects of lncRNA IDH1-AS1 on gliomas. Because overexpressing IDH1-AS1 inhibited cell growth, IDH1-AS1 could also be considered as a potential target for glioma treatment.