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MFN2 suppresses the accumulation of lipid droplets and the progression of clear cell renal cell carcinoma
Cancer Science ( IF 4.5 ) Pub Date : 2024-03-13 , DOI: 10.1111/cas.16151
Zhiduan Cai 1 , Wenjun Luo 1 , Haoran Wang 1, 2 , Rui Zhu 1 , Yaoji Yuan 1 , Xiangyu Zhan 1 , Mengyuan Xie 2 , Haoquan Zhuang 1 , Haoyu Chen 1 , Yuyu Xu 1 , Xiezhao Li 1 , Leyuan Liu 1 , Guibin Xu 1, 3
Cancer Science ( IF 4.5 ) Pub Date : 2024-03-13 , DOI: 10.1111/cas.16151
Zhiduan Cai 1 , Wenjun Luo 1 , Haoran Wang 1, 2 , Rui Zhu 1 , Yaoji Yuan 1 , Xiangyu Zhan 1 , Mengyuan Xie 2 , Haoquan Zhuang 1 , Haoyu Chen 1 , Yuyu Xu 1 , Xiezhao Li 1 , Leyuan Liu 1 , Guibin Xu 1, 3
Affiliation
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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.
中文翻译：
MFN2抑制脂滴的积累和透明细胞肾细胞癌的进展
在苏木精和伊红 (H&E) 染色过程中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透明的肥皂泡，这是透明细胞肾细胞癌 (ccRCC) 的一个关键病理特征。据报道，线粒体动力学与脂质代谢和肿瘤发展密切相关。然而，ccRCC 中线粒体动力学与脂质代谢重编程之间的关系仍有待进一步探讨。我们进行了生物信息学分析，以确定肿瘤和正常组织之间差异表达的调节线粒体动力学的关键基因，并通过免疫组织化学和蛋白质印迹进行确认。确定靶标后，我们创建了稳定的 ccRCC 细胞系，以测试靶基因对线粒体形态、培养细胞和异种移植模型中的肿瘤发生以及脂质代谢谱的影响。研究发现，线粒体融合蛋白 2 (MFN2) 在 ccRCC 组织中表达下调，且与 ccRCC 患者的不良预后相关。 MFN2 抑制 ccRCC 细胞的线粒体断裂、增殖、迁移和侵袭以及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。
更新日期：2024-03-13
中文翻译：
MFN2抑制脂滴的积累和透明细胞肾细胞癌的进展
在苏木精和伊红 (H&E) 染色过程中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透明的肥皂泡，这是透明细胞肾细胞癌 (ccRCC) 的一个关键病理特征。据报道，线粒体动力学与脂质代谢和肿瘤发展密切相关。然而，ccRCC 中线粒体动力学与脂质代谢重编程之间的关系仍有待进一步探讨。我们进行了生物信息学分析，以确定肿瘤和正常组织之间差异表达的调节线粒体动力学的关键基因，并通过免疫组织化学和蛋白质印迹进行确认。确定靶标后，我们创建了稳定的 ccRCC 细胞系，以测试靶基因对线粒体形态、培养细胞和异种移植模型中的肿瘤发生以及脂质代谢谱的影响。研究发现，线粒体融合蛋白 2 (MFN2) 在 ccRCC 组织中表达下调，且与 ccRCC 患者的不良预后相关。 MFN2 抑制 ccRCC 细胞的线粒体断裂、增殖、迁移和侵袭以及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。
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