PLEKHA4 is transcriptionally regulated by HOXD9 and regulates glycolytic reprogramming and progression in glioblastoma via activation of the STAT3/SOCS-1 pathway.

IF 5.9 2区 医学 Q1 ONCOLOGY
Dainan Zhang, Xiaoyin Wang, Meng Xiao, Shunchang Ma, Shaomin Li, Wang Jia
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引用次数: 0

Abstract

Recent studies have demonstrated that PLEKHA4 promotes tumor growth in some cancers, such as small-cell lung cancer, melanoma, and hepatic carcinomas; however, the underlying mechanism in glioblastoma remains ambiguous. Bioinformatic was used to analysis PLEKHA4 expression. In vitro and in vivo experiments were conducted to detect the effect of PLEKHA4 on glioblastoma cell glycolytic reprogramming and progression. GSEA was used to analyze the signal pathways related to PLEKHA4. Pharmacological methods further validated the role of activation pathways. We evaluated the effects of PLEKHA4 knockdown combined with temozolomide (TMZ) on glioblastoma cell proliferation and apoptosis in vitro and in vivo. We observed an overexpression of PLEKHA4 in GBM cell lines, resulting in enhanced cell proliferation, inhibited apoptosis, and promoted glycolysis. Mechanistically, our study demonstrated that PLEKHA4 mediates cell proliferation, apoptosis, and glycolysis via the STAT3/SOCS1 signaling pathway. Additionally, HOXD9 was predicted using Jasper, which is a transcription factor that binds to the PLEKHA4 promoter region. Knocking down PLEKHA4 combined with TMZ inhibited cell proliferation and promoted cell apoptosis in vitro and in vivo. Our results indicated that HOXD9-medicated PLEKHA4 regulates glioblastoma cell proliferation and glycolysis via activation of the STAT3/SOCS1 pathway.

PLEKHA4受HOXD9的转录调控,并通过激活STAT3/SOCS-1通路调控胶质母细胞瘤的糖酵解重编程和进展。
最近的研究表明PLEKHA4促进某些癌症的肿瘤生长,如小细胞肺癌、黑色素瘤和肝癌;然而,胶质母细胞瘤的潜在机制仍不清楚。应用生物信息学方法分析PLEKHA4的表达。通过体外和体内实验检测PLEKHA4对胶质母细胞瘤细胞糖酵解重编程和进展的影响。使用GSEA分析PLEKHA4相关的信号通路。药理学方法进一步验证了激活途径的作用。我们在体外和体内研究了PLEKHA4敲低联合替莫唑胺(temozolomide, TMZ)对胶质母细胞瘤细胞增殖和凋亡的影响。我们观察到PLEKHA4在GBM细胞系中过表达,导致细胞增殖增强,抑制细胞凋亡,促进糖酵解。在机制上,我们的研究表明PLEKHA4通过STAT3/SOCS1信号通路介导细胞增殖、凋亡和糖酵解。此外,使用Jasper预测HOXD9, Jasper是一种结合PLEKHA4启动子区域的转录因子。敲低PLEKHA4与TMZ联合抑制细胞增殖,促进细胞凋亡。我们的研究结果表明,hoxd9药物PLEKHA4通过激活STAT3/SOCS1途径调节胶质母细胞瘤细胞增殖和糖酵解。
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来源期刊
Oncogenesis
Oncogenesis ONCOLOGY-
CiteScore
11.90
自引率
0.00%
发文量
70
审稿时长
26 weeks
期刊介绍: Oncogenesis is a peer-reviewed open access online journal that publishes full-length papers, reviews, and short communications exploring the molecular basis of cancer and related phenomena. It seeks to promote diverse and integrated areas of molecular biology, cell biology, oncology, and genetics.
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