1. LINC00978 regulates metabolic rewiring to promote the malignancy of glioblastoma through AKR1B1.
- Author
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Meng M, Yang L, Zhou H, Cheng Q, Peng R, Wang Z, Liang X, Wen J, Nie J, Hu Z, Zhang L, and Liu Z
- Subjects
- Humans, Cell Proliferation genetics, Down-Regulation, Deoxyglucose, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Aldehyde Reductase genetics, Aldehyde Reductase metabolism, Glioblastoma pathology, Glioma genetics, Brain Neoplasms pathology
- Abstract
Glioma is a fatal primary brain tumor. Improved glioma treatment effectiveness depends on a better understanding of its underlying mechanisms. Glioblastoma (GBM), was classified as high-grade glioma with the most lethality and therapeutic resistance. Herein, we reported LINC00978 overexpressed in high-grade gliomas. Down-regulation of LINC00978 in glioblastoma cells inhibited cell proliferation, invasion, migration, and induced apoptosis. In vivo experiments confirmed that the CamK-A siRNA of LINC00978 could effectively inhibit the proliferation of glioblastoma cells. The main pathway and genes regulated by LINC00978 were detected using RNA sequencing to elucidate the molecular mechanism. The results suggest that LINC00978 regulates the expression of genes related to metabolic pathways, including aldo-keto reductase family 1 member B (AKR1B1), which mediates the cytotoxicity of 2-deoxyglucose. LINC00978 positively regulated AKR1B1 expression, and 2-deoxyglucose induced AKR1B1 expression via a LINC00978-dependent mechanism. This research has revealed that LINC00978 promotes the sensitivity of glioblastoma cells to 2DG. LINC00978 is highly expressed in most high-grade glioma patients. Thus, understanding the anticancer mechanism identified in this study may contribute to treating the majority of glioma patients. This study clarified the function and molecular mechanism of LINC00978 in glioblastoma and provided a study basis for LINC00978 to guide the clinical treatment of glioblastoma., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work. There is no professional or other personal interest of any nature or kind in any product service and/or company that could be constructed. As influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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