干扰 MTHFD2 可通过 ERK 信号诱导卵巢癌细胞中的铁变态反应,从而抑制肿瘤的恶性进展。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-06-01 Epub Date: 2024-03-15 DOI:10.1007/s10863-024-10014-1
Xiaoliang Mo, Qianqian Liu, Kunling Liang, Yingxin Song
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引用次数: 0

摘要

卵巢癌(OC)是死亡率最高的致命妇科癌症。亚甲基四氢叶酸脱氢酶 2(MTHFD2)是一种重要的肿瘤促进因子,在包括 OC 在内的多种恶性肿瘤中过度表达。本研究旨在探讨MTHFD2在OC恶性进展中的作用和机制。因此,通过CCK-8检测法、EdU检测法、流式细胞术、伤口愈合、Transwell检测法和Western印迹法对细胞增殖、循环、凋亡、迁移和侵袭进行了评估。此外,还通过测量葡萄糖和乳酸的产生水平以及 GLUT1、HK2 和 PKM2 的表达来评估糖酵解。然后用 Western 印迹法检测铁变态相关蛋白和 ERK 信号的表达。通过测量铁水平、GSH、MDA和ROS活性来检测铁变态反应。结果显示,MTHFD2 在 OC 细胞中高表达。此外,干扰 MTHFD2 会诱导 OC 细胞发生铁变态反应、促进 ROS 积累、破坏线粒体功能、降低 ATP 含量并抑制糖酵解。随后,我们进一步发现,干扰 MTHFD2 会通过 ERK 信号转导影响 OC 细胞的线粒体功能和糖酵解。此外,干扰 MTHFD2 还会影响铁突变,从而抑制 OC 细胞的恶性发展。综上所述,本研究揭示了干扰MTHFD2可通过调节ERK信号传导诱导OC中的铁变态反应,从而抑制肿瘤的恶性进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Interference with MTHFD2 induces ferroptosis in ovarian cancer cells through ERK signaling to suppress tumor malignant progression.

Ovarian cancer (OC) is a deadliest gynecological cancer with the highest mortality rate. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a crucial tumor-promoting factor, is over-expressed in several malignancies including OC. The present study aimed to explore the role and mechanisms of MTHFD2 in OC malignant progression. Thus, cell proliferation, cycling, apoptosis, migration, and invasion were evaluated by CCK-8 assay, EdU assay, flow cytometry, wound healing, transwell assay and western blotting. Additionally, glycolysis was assessed by measuring the level of glucose and lactate production, as well as the expressions of GLUT1, HK2 and PKM2. Then the expression of ferroptosis-related proteins and ERK signaling was detected using western blotting. Ferroptosis was detected through the measurement of iron level, GSH, MDA and ROS activities. The results revealed that MTHFD2 was highly expressed in OC cells. Besides, interference with MTHFD2 induced ferroptosis, promoted ROS accumulation, destroyed mitochondrial function, reduced ATP content and inhibited glycolysis in OC cells. Subsequently, we further found that interference with MTHFD2 affected mitochondrial function and glycolysis in OC cells through ERK signaling. Moreover, interference with MTHFD2 affected ferroptosis to inhibit the malignant progression of OC cells. Collectively, our present study disclosed that interference with MTHFD2 induced ferroptosis in OC to inhibit tumor malignant progression through regulating ERK signaling.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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