GNAS, not a Highly Mutated Gene, Has Prognostic Significance and Carcinogenic Effects in Osteosarcoma.

IF 2.5 Q3 CELL BIOLOGY Cellular Physiology and Biochemistry Pub Date : 2024-09-15 DOI:10.33594/000000728
Jin Qi, Yanjiao Huang, Yaogang Bian
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Abstract

Background/aims: Osteosarcoma is a prevalent and aggressive primary malignant bone tumor affecting children and adolescents. Despite advancements in sequencing technologies, there remains a lack of reliable prognostic biomarkers and effective targeted therapies for osteosarcoma. This study focuses on identifying key prognostic genes, particularly the role of GNAS, in osteosarcoma progression.

Methods: Bioinformatics analyses were performed on osteosarcoma datasets from the Gene Expression Omnibus (GEO). Differential gene expression analysis, weighted correlation network analysis (WGCNA), and survival analysis identified potential prognostic hub genes. The expression and function of these genes were validated through immunohistochemistry and animal experiments. Specifically, the role of GNAS was investigated through siRNA-mediated knockdown in osteosarcoma cell lines and nude mice models.

Results: Five hub genes (PROP1, GNAS, CYP4F2, LHX3, CNGB1) were identified as significantly related to osteosarcoma prognosis. Among these, GNAS was found to be highly expressed in osteosarcoma tissues compared to normal tissues. Immunohistochemical analysis confirmed the elevated expression of GNAS in osteosarcoma samples. GNAS mutation analysis revealed a low mutation rate in osteosarcoma, suggesting its oncogenic role is independent of mutational status. Animal experiments demonstrated that knocking down GNAS significantly inhibited tumor growth and induced apoptosis in osteosarcoma cells.

Conclusion: GNAS is highly expressed in osteosarcoma and associated with poor prognosis, acting as an oncogene in osteosarcoma progression. Targeting GNAS could be a potential therapeutic strategy for osteosarcoma. Further studies on GNAS-related signaling pathways may provide deeper insights into the molecular mechanisms driving osteosarcoma malignancy.

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GNAS并非高度突变基因,但在骨肉瘤中具有预后意义和致癌作用。
背景/目的:骨肉瘤是一种常见的侵袭性原发性恶性骨肿瘤,多发于儿童和青少年。尽管测序技术不断进步,但骨肉瘤仍缺乏可靠的预后生物标志物和有效的靶向治疗。本研究的重点是确定关键预后基因,特别是 GNAS 在骨肉瘤进展中的作用:方法:对基因表达总库(GEO)中的骨肉瘤数据集进行生物信息学分析。差异基因表达分析、加权相关网络分析(WGCNA)和生存分析确定了潜在的预后枢纽基因。通过免疫组化和动物实验验证了这些基因的表达和功能。特别是,通过 siRNA 介导的骨肉瘤细胞系和裸鼠模型敲除,研究了 GNAS 的作用:结果:五个枢纽基因(PROP1、GNAS、CYP4F2、LHX3、CNGB1)与骨肉瘤预后显著相关。其中,与正常组织相比,GNAS在骨肉瘤组织中高表达。免疫组化分析证实了骨肉瘤样本中GNAS的高表达。GNAS突变分析显示,骨肉瘤中的突变率较低,表明其致癌作用与突变状态无关。动物实验表明,敲除 GNAS 能显著抑制肿瘤生长并诱导骨肉瘤细胞凋亡:结论:GNAS在骨肉瘤中高表达,与预后不良有关,是骨肉瘤发展过程中的致癌基因。靶向 GNAS 可能是骨肉瘤的一种潜在治疗策略。对GNAS相关信号通路的进一步研究可能会让人们对骨肉瘤恶性发展的分子机制有更深入的了解。
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来源期刊
CiteScore
5.80
自引率
0.00%
发文量
86
审稿时长
1 months
期刊介绍: Cellular Physiology and Biochemistry is a multidisciplinary scientific forum dedicated to advancing the frontiers of basic cellular research. It addresses scientists from both the physiological and biochemical disciplines as well as related fields such as genetics, molecular biology, pathophysiology, pathobiochemistry and cellular toxicology & pharmacology. Original papers and reviews on the mechanisms of intracellular transmission, cellular metabolism, cell growth, differentiation and death, ion channels and carriers, and the maintenance, regulation and disturbances of cell volume are presented. Appearing monthly under peer review, Cellular Physiology and Biochemistry takes an active role in the concerted international effort to unravel the mechanisms of cellular function.
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