下調MTHFD2通過抑制周期相關基因抑制NSCLC進展

2019年4月，溫州醫科大學**附屬醫院肺內科心肺重點實驗室；溫州醫科大學**附屬醫院介入治療科；溫州醫科大學**附屬醫院胸心血管科；溫州醫科大學藥學院化學生物學研究中心(Key Laboratory of Heart and Lung, Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University,Wenzhou, China；Interventional Therapy Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China；Department of Thoracic Cardiovascular, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China；Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China) Chengguang Zhao老師研究團隊在《JOURNAL OF CELLULAR AND MOLECULAR MEDICINE》上發表論文：

“Down-regulation of MTHFD2 inhibits NSCLC progression by suppressing cycle-related genes”

“下調MTHFD2通過抑制周期相關基因抑制NSCLC進展”

Abstract：

Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a bifunctional enzyme located in the mitochondria. It has been reported to be overexpressed in several malignancies. However, the relationship between the expression of MTHFD2 and non-small cell lung cancer (NSCLC) remains largely unknown. In this study, we found that MTHFD2 was significantly overexpressed in NSCLC tissues and cell lines. Knockdown of MTHFD2 resulted in reduced cell growth and tumorigenicity in vitro and in vivo. Besides, the mRNA and protein expression level of cell cycle genes, such as CCNA2, MCM7 and SKP2, was decreased in MTHFD2 knockdown H1299 cells. Our results indicate that the inhibitory effect of MTHFD2 knockdown on NSCLC may be mediated via suppressing cell cycle-related genes. These findings delineate the role of MTHFD2 in the development of NSCLC and may have potential applications in the treatment of NSCLC.

摘要：

亞甲基四氫葉酸脫氫酶2 (MTHFD2)是一種位于線粒體中的雙功能酶。據報道，它在幾種惡性腫瘤中過表達。然而，MTHFD2表達與非小細胞肺癌(NSCLC)之間的關系在很大程度上仍然未知。在本研究中，我們發現MTHFD2在NSCLC組織和細胞系中顯著過表達。敲低MTHFD2可導致細胞生長和體內外致瘤性降低。此外，MTHFD2敲除H1299細胞后，細胞周期基因CCNA2、MCM7、SKP2 mRNA和蛋白表達水平降低。我們的研究結果表明，MTHFD2敲低對NSCLC的抑制作用可能是通過抑制細胞周期相關基因介導的。這些發現描述了MTHFD2在非小細胞肺癌發展中的作用，并可能在非小細胞肺癌的治療中有潛在的應用。

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