SOGA1 drives ovarian cancer progression via regulation of GNAI1 and activation of the TNF/NF-κB pathway

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene Pub Date : 2025-09-27 DOI:10.1016/j.gene.2025.149800

Tengfei Long , Xuqing Li , Youwei Zhou , Chengcheng Zhu , Minmin Zhang , Min Li , Zhaolian Wei

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引用次数: 0

Abstract

Background

Ovarian cancer (OC) poses a significant public health challenge due to its dismal prognosis and low survival rates. However, the mechanism of OC development remains unclear.

Methods

Transcriptomic data from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases underwent analysis to identify hub programmed cell death (PCD) genes in OC samples compared to normal controls, utilizing weighted gene co-expression network analysis (WGCNA) and Machine learning models. Then, conduct pan-cancer analysis and nomogram on the hub gene Suppressor Of Glucose, Autophagy Associated 1 (SOGA1). The expression levels of the SOGA1 gene were assessed in clinical samples through Reverse Transcription-Quantitative Real-time Polymerase Chain Reaction (RT-qPCR) experiments. Subsequently, Western Blot (WB), Cell Counting Kit-8 (CCK8), Terminal Deoxynucleotidyl Transferase-Mediated dUTP Nick End Labeling (Tunel) wound healing tests, transwell, RNA sequencing, and subcutaneous tumorigenesis in C57BL/6 mice were conducted to investigate the correlation between SOGA1 and OC cell proliferation, invasion, migration, and other functions, as well as the underlying mechanisms.

Results

Through integrated bioinformatics analyses, SOGA1 emerged as a hub gene of PCD in OC. Overexpression of SOGA1 correlated with poor prognosis across multiple cancers, including OC, and served as an independent prognostic factor. The developed nomogram, incorporating SOGA1 expression, accurately predicted overall survival (OS) in OC patients. SOGA1 was significantly upregulated in OC tissues, and high expression of SOGA1 was significantly correlated with lymph node metastasis. Both in vitro and in vivo, modulation of SOGA1 expression led to changes in OC cell proliferation, and SOGA1 promoted OC cell invasion, migration and inhibit apoptosis and inhibit apopapoptosis in vitro. Mechanistically, we found that SOGA1 regulates the Guanine Nucleotide-Binding Protein G (I) Subunit Alpha-1 (GNAI1) protein and facilitates TNF-alpha / NFκB signaling.

Conclusion

This study has confirmed that SOGA1 can regulate the progression of the disease by influencing the TNF signaling pathway according to regulate GNAI1 expression.

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SOGA1通过调节GNAI1和激活TNF/NF-κB通路驱动卵巢癌进展。

背景：卵巢癌（OC）由于其预后不佳和生存率低，对公共卫生构成了重大挑战。然而，OC的发生机制尚不清楚。方法：利用加权基因共表达网络分析（WGCNA）和机器学习模型，对来自癌症基因组图谱（TCGA）和基因型组织表达（GTEx）数据库的转录组学数据进行分析，以确定与正常对照组相比，OC样本中的中心程序性细胞死亡（PCD）基因。然后，对枢纽基因葡萄糖抑制因子Autophagy Associated 1 （SOGA1）进行泛癌分析和nomogram。通过逆转录-实时定量聚合酶链反应（RT-qPCR）实验检测临床样品中SOGA1基因的表达水平。随后，通过Western Blot （WB）、Cell Counting Kit-8 （CCK8）、Terminal Deoxynucleotidyl Transferase-Mediated dUTP Nick End Labeling （Tunel）创面愈合试验、transwell、RNA测序、C57BL/6小鼠皮下肿瘤发生等方法研究SOGA1与OC细胞增殖、侵袭、迁移等功能的相关性及其机制。结果：通过综合生物信息学分析，SOGA1是OC中PCD的枢纽基因。SOGA1过表达与多种癌症（包括OC）的不良预后相关，是一个独立的预后因素。纳入SOGA1表达的已开发的nomogram （nomogram）能够准确预测OC患者的总生存期（OS）。SOGA1在OC组织中显著上调，且SOGA1的高表达与淋巴结转移显著相关。在体外和体内实验中，SOGA1表达的调节导致OC细胞增殖发生变化，SOGA1促进OC细胞在体外的侵袭和迁移。在机制上，我们发现SOGA1调节鸟嘌呤核苷酸结合蛋白G (I)亚单位α -1 （GNAI1）蛋白，促进tnf - α / NFκB信号传导。结论：本研究证实SOGA1可通过调节GNAI1的表达，通过影响TNF信号通路调节疾病的进展。

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

Gene 生物-遗传学

CiteScore

6.10

自引率

2.90%

发文量

718

审稿时长

42 days

期刊介绍： Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.