PDF(Pubmed)
Abstract：
Dissolving the lipid droplets in tissue section with alcohol during a hematoxylin and eosin (H&E) stain causes the tumor cells to appear like clear soap bubbles under a microscope, which is a key pathological feature of clear cell renal cell carcinoma (ccRCC). Mitochondrial dynamics have been reported to be closely associated with lipid metabolism and tumor development. However, the relationship between mitochondrial dynamics and lipid metabolism reprogramming in ccRCC remains to be further explored. We conducted bioinformatics analysis to identify key genes regulating mitochondrial dynamics differentially expressed between tumor and normal tissues and immunohistochemistry and Western blot to confirm. After the target was identified, we created stable ccRCC cell lines to test the impact of the target gene on mitochondrial morphology, tumorigenesis in culture cells and xenograft models, and profiles of lipid metabolism. It was found that mitofusin 2 (MFN2) was downregulated in ccRCC tissues and associated with poor prognosis in patients with ccRCC. MFN2 suppressed mitochondrial fragmentation, proliferation, migration, and invasion of ccRCC cells and growth of xenograft tumors. Furthermore, MFN2 impacted lipid metabolism and reduced the accumulation of lipid droplets in ccRCC cells. MFN2 suppressed disease progression and improved prognosis for patients with ccRCC possibly by interrupting cellular lipid metabolism and reducing accumulation of lipid droplets.
摘要：
在苏木精和伊红（H＆E）染色期间，用酒精溶解组织切片中的脂滴会导致肿瘤细胞在显微镜下看起来像清晰的肥皂泡，是肾透明细胞癌的重要病理特征。线粒体动力学已被报道与脂质代谢和肿瘤的发展密切相关。然而,线粒体动力学与ccRCC脂质代谢重编程之间的关系还有待进一步探讨。我们进行了生物信息学分析，以确定调节肿瘤和正常组织之间线粒体动力学差异表达的关键基因，并进行免疫组织化学和Westernblot确认。确定目标后,我们创建了稳定的ccRCC细胞系来测试靶基因对线粒体形态的影响，培养细胞和异种移植模型中的肿瘤发生，和脂质代谢的概况。发现mitofusin2（MFN2）在ccRCC组织中下调，并与ccRCC患者的不良预后有关。MFN2抑制线粒体片段化，扩散,迁移,ccRCC细胞的侵袭和异种移植肿瘤的生长。此外，MFN2影响脂质代谢并减少ccRCC细胞中脂滴的积累。MFN2可能通过中断细胞脂质代谢和减少脂滴积累来抑制ccRCC患者的疾病进展并改善预后。
