LINC00978 regulates metabolic rewiring to promote the malignancy of glioblastoma through AKR1B1

Ming Meng; Liting Yang; Hongshu Zhou; Quan Cheng; Renjun Peng; Zeyu Wang; Xisong Liang; Jie Wen; Jilin Nie; Zhongliang Hu; Liyang Zhang; Zhixiong Liu

doi:10.1016/j.canlet.2023.216277

LINC00978 regulates metabolic rewiring to promote the malignancy of glioblastoma through AKR1B1

Cancer Lett. 2023 Jul 28:567:216277. doi: 10.1016/j.canlet.2023.216277. Epub 2023 Jun 17.

Authors

Ming Meng¹, Liting Yang², Hongshu Zhou³, Quan Cheng⁴, Renjun Peng⁵, Zeyu Wang⁶, Xisong Liang⁷, Jie Wen⁸, Jilin Nie⁹, Zhongliang Hu¹⁰, Liyang Zhang¹¹, Zhixiong Liu¹²

Affiliations

¹ Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; Hypothalamic Pituitary Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China. Electronic address: mengming@csu.edu.cn.
² Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; Hypothalamic Pituitary Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China. Electronic address: yanglt@csu.edu.cn.
³ Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; Hypothalamic Pituitary Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China. Electronic address: zhou_hs@csu.edu.cn.
⁴ Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; Hypothalamic Pituitary Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China. Electronic address: chengquan@csu.edu.cn.
⁵ Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; Hypothalamic Pituitary Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China. Electronic address: prjscience@csu.edu.cn.
⁶ Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; Hypothalamic Pituitary Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China. Electronic address: zeyu.wang@ed.ac.uk.
⁷ Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; Hypothalamic Pituitary Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China. Electronic address: xisongliang@csu.edu.cn.
⁸ Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; Hypothalamic Pituitary Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China. Electronic address: 218111098@csu.edu.cn.
⁹ Department of Radiology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China. Electronic address: 348158933@qq.com.
¹⁰ Clinical Diagnosis and Therapy Center for Glioma of Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; Department of Radiology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China. Electronic address: huzhongliang@csu.edu.cn.
¹¹ Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; Hypothalamic Pituitary Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; Clinical Diagnosis and Therapy Center for Glioma of Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China. Electronic address: zhangliyang@csu.edu.cn.
¹² Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; Hypothalamic Pituitary Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, China. Electronic address: zhixiongliu@csu.edu.cn.

PMID: 37336288
DOI: 10.1016/j.canlet.2023.216277

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.

Keywords: 2-Deoxyglucose; AKR1B1; Glioblastoma; LINC00978; Long non-coding RNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aldehyde Reductase / genetics
Aldehyde Reductase / metabolism
Brain Neoplasms* / pathology
Cell Line, Tumor
Cell Proliferation / genetics
Deoxyglucose
Down-Regulation
Gene Expression Regulation, Neoplastic
Glioblastoma* / pathology
Glioma* / genetics
Humans

Substances

Deoxyglucose
AKR1B1 protein, human
Aldehyde Reductase