LncARSR promotes glioma tumor growth by mediating glycolysis through the STAT3/HK2 axis

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2024-05-29 DOI:10.1016/j.cyto.2024.156663

Zhenyang Tian , Qi Dai , Bin Liu , Hui Lin , Huiping Ou

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引用次数: 0

Abstract

Background

Glioma represents the predominant malignant brain tumor. This investigation endeavors to elucidate the impact and prospective mechanisms of glycolysis-related lncARSR on glioma.

Methods

LncARSR level was assessed in normal glial cells and glioma cells. Cell proliferation, migration, and invasion measurements were conducted through CCK-8, wound healing, and transwell assay. Flow cytometry was utilized to measure cell apoptosis and cell cycle. Biochemical assay kits and immunoblotting were employed to measure the content of glycolysis-related indicators and protein expression, respectively. We analyzed the impact of both lncARSR knockdown and overexpression of the Signal Transducer and Activator of Transcription 3 (STAT3) on Hexokinase 2 (HK2) using dual luciferase reporter assays and Chromatin Immunoprecipitation (ChIP) experiments. Further assessment of the impact of lncARSR on glioma progression was conducted through animal experiments.

Results

LncARSR was expressed at elevated levels in glioma cells compared to normal glial cells. Overexpressing lncARSR enhanced proliferation, migration, invasion, and G2/M phase arrest in glioma cells and also increased glucose, lactate, ATP production, as well as the expression of HK2, PFK1, PKM2, GLUT1, and LDHA. STAT3 binding to the HK2 gene promoter was weakened following the knockdown of lncARSR. Upregulation of STAT3 reversed the suppressed functions of knocking down lncARSR on cell proliferation, migration, invasion, G2/M phase arrest, and glycolysis and counteracted its promotional effect on cell apoptosis. In vivo, knocking down lncARSR inhibits glioma growth and ki67 and PCNA expression.

Conclusion

LncARSR promotes the development of glioma by enhancing glycolysis through the STAT3-HK2 axis.

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LncARSR 通过 STAT3/HK2 轴介导糖酵解促进胶质瘤肿瘤生长

背景胶质瘤是最主要的恶性脑肿瘤。本研究试图阐明与糖酵解相关的 lncARSR 对胶质瘤的影响和前瞻性机制。通过CCK-8、伤口愈合和透孔试验进行细胞增殖、迁移和侵袭测量。流式细胞术用于测量细胞凋亡和细胞周期。生化检测试剂盒和免疫印迹法分别用于测量糖酵解相关指标的含量和蛋白质的表达。我们利用双荧光素酶报告实验和染色质免疫沉淀（ChIP）实验分析了lncARSR敲除和信号转导和转录激活因子3（STAT3）过表达对六磷酸酶2（HK2）的影响。结果与正常胶质细胞相比，lncARSR在胶质瘤细胞中的表达水平升高。过表达lncARSR能增强胶质瘤细胞的增殖、迁移、侵袭和G2/M期停滞，还能增加葡萄糖、乳酸和ATP的产生，以及HK2、PFK1、PKM2、GLUT1和LDHA的表达。敲除 lncARSR 后，STAT3 与 HK2 基因启动子的结合减弱。STAT3的上调逆转了敲除lncARSR对细胞增殖、迁移、侵袭、G2/M期停滞和糖酵解的抑制作用，并抵消了其对细胞凋亡的促进作用。结论lncARSR通过STAT3-HK2轴促进糖酵解，从而促进胶质瘤的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.