OSBPL10-CNBP轴介导缺氧诱导的胰腺癌发展

IF 5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
BioFactors Pub Date : 2024-09-27 DOI:10.1002/biof.2124
Yishu Huang, Ronghao Zhang, Shuyang Fan, Minmin Shi, Xiaomei Tang, Xinjing Wang, Xiaxing Deng
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引用次数: 0

摘要

胰腺导管腺癌(PDAC)是消化系统肿瘤中预后最差的恶性肿瘤之一。鉴定新型生物标志物对胰腺癌患者的治疗研究和预后预测具有重要意义。由于 OSBPL10 在其他肿瘤中参与致癌活动,我们阐明了它对胰腺癌进展的作用机制。我们利用基因表达总库数据库中的数据检测 OSBPL10 在正常组织和胰腺癌组织中的表达。我们进行了一系列实验来评估 OSBPL10 对胰腺癌细胞增殖和转移能力的影响,并通过流式细胞术评估了 OSBPL10 对巨噬细胞的影响。此外,我们还利用共免疫共沉淀、质谱分析和免疫印迹法研究了OSBPL10活性的潜在机制。我们的研究发现,OSBPL10在胰腺癌中上调,预后较差。OSBPL10的过表达促进了胰腺癌细胞的恶性行为,并通过刺激M1巨噬细胞转化为M2巨噬细胞对肿瘤免疫微环境产生影响。从机理上讲,缺氧通过缺氧诱导因子1-α与OSBPL10启动子区域的相互作用诱导OSBPL10的表达。此外,OSBPL10直接与CNBP结合,介导CNBP的表达,最终调节胰腺癌细胞的增殖和转移能力,并影响巨噬细胞的极化。研究强调了OSBPL10在胰腺癌中的致癌作用,揭示了涉及缺氧、HIF-1α和CNBP的关键机制。研究结果表明,OSBPL10是胰腺癌的一种新型生物标志物,使其成为干预这种恶性肿瘤的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
OSBPL10-CNBP axis mediates hypoxia-induced pancreatic cancer development.

Pancreatic ductal adenocarcinoma (PDAC) is one of malignancies with worst outcomes among digestive system tumors. Identification of novel biomarkers is of great significance for treatment researches and prognosis prediction of pancreatic cancer patients. Due to OSBPL10 known involvement in oncogenic activity in other tumors, we elucidated the mechanism underlying its contribution to pancreatic cancer progression. We employed data from the Gene Expression Omnibus database to detect the expression of OSBPL10 in normal and pancreatic cancer tissues. A series of assays were conducted to assess the impact of OSBPL10 on the proliferation and metastatic capacities of pancreatic cancer cells and the influence of OSBPL10 on macrophages were evaluated by Flow cytometry. In addition, Co-immunoprecipitation, mass spectrometry, and western blot assays were utilized to investigate the potential mechanisms of OSBPL10 activity. From our study, OSBPL10 is revealed to be upregulated in pancreatic cancer, with poor prognosis. The overexpression promotes malignant behaviors of pancreatic cancer cells and has an impact on tumor immune microenvironment by stimulating the transformation M1 macrophages into M2 macrophages. Mechanistically, hypoxia induces the expression of OSBPL10 through interaction between hypoxia-inducible factor 1-α and the promoter region of OSBPL10. Additionally, OSBPL10 directly bound to CNBP, mediating CNBP expression and ultimately regulating the proliferation and metastasis capacity of pancreatic cancer cells, as well as influencing macrophage polarization. The research emphasized the oncogenic role of OSBPL10 in pancreatic cancer, uncovering key mechanisms involving hypoxia, HIF-1α, and CNBP. The finding suggests that OSBPL10 is a novel biomarker in pancreatic cancer, making it a potential therapeutic target for intervention in this malignancy.

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来源期刊
BioFactors
BioFactors 生物-内分泌学与代谢
CiteScore
11.50
自引率
3.30%
发文量
96
审稿时长
6-12 weeks
期刊介绍: BioFactors, a journal of the International Union of Biochemistry and Molecular Biology, is devoted to the rapid publication of highly significant original research articles and reviews in experimental biology in health and disease. The word “biofactors” refers to the many compounds that regulate biological functions. Biological factors comprise many molecules produced or modified by living organisms, and present in many essential systems like the blood, the nervous or immunological systems. A non-exhaustive list of biological factors includes neurotransmitters, cytokines, chemokines, hormones, coagulation factors, transcription factors, signaling molecules, receptor ligands and many more. In the group of biofactors we can accommodate several classical molecules not synthetized in the body such as vitamins, micronutrients or essential trace elements. In keeping with this unified view of biochemistry, BioFactors publishes research dealing with the identification of new substances and the elucidation of their functions at the biophysical, biochemical, cellular and human level as well as studies revealing novel functions of already known biofactors. The journal encourages the submission of studies that use biochemistry, biophysics, cell and molecular biology and/or cell signaling approaches.
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