1. LncRNA LINC00998 inhibits the malignant glioma phenotype via the CBX3-mediated c-Met/Akt/mTOR axis.
- Author
-
Cai H, Yu Y, Ni X, Li C, Hu Y, Wang J, Chen F, Xi S, and Chen Z
- Subjects
- Brain Neoplasms pathology, Cell Line, Tumor, Cell Proliferation genetics, Down-Regulation genetics, Gene Expression Regulation, Neoplastic, Glioma pathology, Histones metabolism, Humans, Methylation, MicroRNAs genetics, MicroRNAs metabolism, Phenotype, Promoter Regions, Genetic genetics, Proteolysis, Proto-Oncogene Proteins c-akt antagonists & inhibitors, Proto-Oncogene Proteins c-met genetics, RNA, Long Noncoding genetics, Survival Analysis, Ubiquitination, Brain Neoplasms genetics, Chromosomal Proteins, Non-Histone metabolism, Glioma genetics, Proto-Oncogene Proteins c-akt metabolism, Proto-Oncogene Proteins c-met metabolism, RNA, Long Noncoding metabolism, Signal Transduction, TOR Serine-Threonine Kinases metabolism
- Abstract
Long noncoding RNAs (lncRNAs), once considered to be nonfunctional relics of evolution, are emerging as essential genes in tumor progression. However, the function and underlying mechanisms of lncRNAs in glioma remain unclear. This study aimed to investigate the role of LINC00998 in glioma progression. Through screening using TCGA database, we found that LINC00998 was downregulated in glioblastoma tissues and that low expression of LINC00998 was associated with poor prognosis. Overexpression of LINC00998 inhibited glioma cell proliferation in vitro and in vivo and blocked the G1/S cell cycle transition, which exerted a tumor-suppressive effect on glioma progression. Mechanistically, RNA pull-down and mass spectrometry results showed an interaction between LINC00998 and CBX3. IP assays demonstrated that LINC00998 could stabilize CBX3 and prevent its ubiquitination degradation. GSEA indicated that LINC00998 could regulate the c-Met/Akt/mTOR signaling pathway, which was further confirmed by a rescue assay using siRNA-mediated knockdown of CBX3 and the Akt inhibitor MK2206. In addition, dual-luciferase assays showed that miR-34c-5p could directly bind to LINC00998 and downregulate its expression. Our results identified LINC00998 as a novel tumor suppressor in glioma, and LINC00998 could be a novel prognostic biomarker, providing a strategy for precision therapy in glioma patients.
- Published
- 2020
- Full Text
- View/download PDF