eb病毒调节铁代谢和铁蛋白表达促进胃癌发生。

IF 2.9 4区 生物学 Q3 CELL BIOLOGY
Xia Zhao, Duo Shi, Lingling Sun, Zhiyuan Gong, Wen Liu, Yan Zhang, Bing Luo
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引用次数: 0

摘要

铁对细胞存活和维持正常生理功能至关重要。病毒感染会破坏细胞铁代谢,导致炎症和癌症。铁蛋白是一种关键的铁结合蛋白,由铁蛋白重链1 (FTH1)和铁蛋白轻链(FTL)组成,有助于调节全身铁平衡,两者都与各种肿瘤的发展有关。eb病毒(EBV)是第一个在人类中发现的致癌病毒,可诱导EBV相关胃癌(EBVaGC)的发展。然而,FTH1和FTL在EBVaGC中的调控机制和功能尚不清楚。本研究旨在探讨EBV如何调控FTH1和FTL及其在EBVaGC发育中的作用。我们发现EBV能够重塑细胞内铁代谢,影响FTH1和FTL的表达。ebv编码的LMP2A通过上调p62,阻断自噬降解通路,促进FTH1和FTL的表达,从而参与EBVaGC的发生发展。敲低FTL抑制细胞迁移和增殖,促进细胞凋亡,而敲低FTH1对这些细胞功能的影响可以忽略不计。此外,我们发现铁蛋白增强了胃癌细胞的炎症状态。总的来说,我们的研究结果强调了EBV对铁蛋白的重要影响,强调了铁蛋白在EBVaGC进展中以前未被认识到的作用。这一新途径可能为EBVaGC的治疗提供新的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Epstein-Barr virus modulates iron metabolism and ferritin expression to promote tumorigenesis in gastric cancer.

Iron is crucial for cell survival and maintaining normal physiological functions. Viral infections can disrupt cellular iron metabolism, leading to inflammation and cancer. Ferritin, a key iron-binding protein, consists of ferritin heavy chain 1 (FTH1) and ferritin light chain (FTL) and helps regulate systemic iron balance, both implicated in various tumor developments. Epstein-Barr virus (EBV), the first oncogenic virus discovered in humans, can induce the development of EBV-associated gastric cancer (EBVaGC). However, the regulatory mechanisms and functions of FTH1 and FTL in EBVaGC are poorly understood. This study aimed to investigate how EBV regulates FTH1 and FTL and their roles in the development of EBVaGC. We show that EBV is able to remodel intracellular iron metabolism, affecting the expression of FTH1 and FTL. EBV-encoded LMP2A promotes the expression of FTH1 and FTL by up-regulating p62 and blocking the autophagy degradation pathway, thus participating in the occurrence and development of EBVaGC. Knocking down FTL inhibits cell migration and proliferation, and promotes apoptosis, whereas FTH1 knockdown has negligible effects on these cellular functions. Additionally, we found that ferritin enhanced the inflammatory state of gastric cancer cells. Overall, our findings highlight the significant impact of EBV on ferritin, underscoring a previously unrecognized role of ferritin in the progression of EBVaGC. This novel pathway could offer new therapeutic targets for the treatment of EBVaGC.

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来源期刊
Journal of Molecular Histology
Journal of Molecular Histology 生物-细胞生物学
CiteScore
5.90
自引率
0.00%
发文量
68
审稿时长
1 months
期刊介绍: The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.
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