CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Up-regulation of MTHFD2 is associated with clinicopathological characteristics and poor survival in ovarian cancer, possibly by regulating MOB1A signaling.
Up-regulation of MTHFD2 is associated with clinicopathological characteristics and poor survival in ovarian cancer, possibly by regulating MOB1A signaling.
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MTHFD2 作为一种 NAD+依赖性酶，通过上调 MBO1A 加速肿瘤进展，提示该蛋白可能成为卵巢癌未来治疗的独立预后因素和潜在治疗靶点。
MTHFD2是一种叶酸偶联代谢酶，已被证明参与代谢重编程和肿瘤细胞维持增殖能力。然而，MTHFD2在卵巢癌发展中的功能及其潜在分子机制仍不清楚。
使用Oncomine、GEPIA、UCSC、cBioPortal、KM Plotter、TISIDB和TIMER等生物信息学相关网站分析了MTHFD2的表达、各种突变、预后及相关网络信号通路。通过我们自己的卵巢癌样本使用RT-qPCR验证了MTHFD2表达的预后价值。通过CCK-8和transwell实验进一步分析了卵巢癌细胞的迁移和侵袭。进行Western-blot实验以探究MTHFD2和MOB1A的蛋白水平。
我们获得了以下重要结果。(1) 与正常样本相比，MTHFD2在卵巢癌中的表达显著上调。(2) 在卵巢癌患者中，MTHFD2表达较高的患者生存率较低。(3) 卵巢癌样本中MTHFD2的主要突变类型为错义突变。(4) 在体外实验中，敲低MTHFD2可抑制增殖、迁移、侵袭以及MOB1A的表达。
MTHFD2 is a folate-coupled metabolic enzyme, which has been proved to participant in the metabolic reprogramming and tumor cell-sustaining proliferative capacity. However, the function of MTHFD2 in the development of ovarian cancer and its potential molecular mechanisms is still unclear.
The expression, various mutations, prognosis, and related network signaling pathways of MTHFD2 were analyzed using bioinformatics-related websites, including Oncomine, GEPIA, UCSC, cBioPortal, KM Plotter, TISIDB and TIMER. The prognostic value of MTHFD2 expression was validated by our own ovarian cancer samples using RT-qPCR. The migration ad invasion of ovarian cancer cells were further analyzed by CCK-8 and transwell assay. The Western-blot assay was performed to explore the protein levels of MTHFD2 and MOB1A.
We obtained the following important results. (1) MTHFD2 expression was markedly up-regulated in ovarian cancer than normal samples. (2) Among patients with ovarian cancer, those with higher MTHFD2 expression was associated with lower survival rate. (3) The major mutation type of MTHFD2 in ovarian cancer samples was missense mutation. (4) MTHFD2 knockdown inhibited proliferation, migration, invasion, as well as the expression of MOB1A in vitro.
MTHFD2, as a NAD + -dependent enzyme, accelerated tumor progression by up-regulating MBO1A, suggesting that this protein may be an independent prognostic factor and a potential therapeutic target for future ovarian cancer treatments.
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