Extracellular Vesicle-Associated MicroRNA-25-3p Derived from Pancreatic Cancer Cells Promotes Hepatic Stellate Cell Activation and Enhances Cancer Progression.

IF 1.6 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical Genetics Pub Date : 2025-08-21 DOI:10.1007/s10528-025-11186-0

Xuejiao Wu, Rui Shen, Zilin Yang, Yuming Tang, Jia Huang, Weiyan Yao

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引用次数: 0

Abstract

Pancreatic cancer is a highly aggressive malignancy with a poor prognosis, mainly due to late diagnosis and early metastatic spread. The underlying mechanisms of pancreatic cancer metastasis, particularly the role of hepatic stellate cell (HSC) activation, are not fully understood. This study tried to find potential biomarkers for pancreatic cancer progression and prognosis by analyzing extracellular vesicle (EV)-associated miRNA profiles in plasma from pancreatic cancer patients and non-cancer controls. Functional assays, including transfection, western blotting, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA), were used to assess the ability of the identified miRNA to activate HSCs and promote cancer progression. Our findings revealed that miR-25-3p was significantly upregulated in EVs derived from pancreatic cancer patients, correlating with increased metastasis and worse survival outcomes. EV-associated miR-25-3p from metastatic pancreatic cancer cells activated HSCs by regulating the expression of Krüppel-like factor 4 (KLF4). Additionally, activated HSCs secreted vascular endothelial growth factor (VEGF), further driving pancreatic cancer metastasis and progression. These results suggest that miR-25-3p could serve as a novel biomarker for pancreatic cancer progression and a potential therapeutic target to improve patient outcomes.

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胰腺癌细胞外囊泡相关MicroRNA-25-3p促进肝星状细胞活化并促进癌症进展

胰腺癌是一种高度侵袭性的恶性肿瘤，预后差，主要原因是诊断晚，转移扩散早。胰腺癌转移的潜在机制，特别是肝星状细胞（HSC）活化的作用，尚不完全清楚。本研究试图通过分析胰腺癌患者和非癌症对照者血浆中细胞外囊泡（EV）相关miRNA谱，寻找胰腺癌进展和预后的潜在生物标志物。功能测定，包括转染、western blotting、免疫荧光和酶联免疫吸附测定（ELISA），用于评估鉴定的miRNA激活hsc和促进癌症进展的能力。我们的研究结果显示，miR-25-3p在胰腺癌患者衍生的ev中显著上调，与转移增加和生存结果恶化相关。来自转移性胰腺癌细胞的ev相关miR-25-3p通过调节kr ppel样因子4 （KLF4）的表达激活hsc。此外，活化的造血干细胞分泌血管内皮生长因子（VEGF），进一步推动胰腺癌的转移和进展。这些结果表明，miR-25-3p可以作为胰腺癌进展的新型生物标志物和改善患者预后的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochemical Genetics 生物-生化与分子生物学

CiteScore

3.90

自引率

0.00%

发文量

133

审稿时长

4.8 months

期刊介绍： Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.