Up-regulation of MTHFD2 is associated with clinicopathological characteristics and poor survival in ovarian cancer, possibly by regulating MOB1A signaling

Journal of Ovarian Research

Kai Huo¹  Sanyuan Zhang²  Xuan Jing³  Jiaolin Yang³  Huancheng Su³  Xueqing Wu⁴  Xiangrong Cui⁵ 

[1] Breast Surgery Department, Tumor Hospital of Shanxi, Affiliated of Shanxi Medical University, 030000, Taiyuan, China;Clinical Laboratory, The Affiliated People’s Hospital of Shanxi Medical University, 030001, Taiyuan, China;Gynaecology and Obstetrics Department, First Hospital of Shanxi Medical University, 030001, Taiyuan, China;Reproductive Medicine Center, The affiliated Children’s Hospital of Shanxi Medical University, Children’s Hospital of Shanxi, Women Health Center of Shanxi, 030001, Taiyuan, China;Reproductive Medicine Center, The affiliated Children’s Hospital of Shanxi Medical University, Children’s Hospital of Shanxi, Women Health Center of Shanxi, 030001, Taiyuan, China;Gynaecology and Obstetrics Department, First Hospital of Shanxi Medical University, 030001, Taiyuan, China;

关键词: MTHFD2;    Ovarian cancer;    Prognosis;    MOB1A;   

DOI  :  10.1186/s13048-022-00954-w

来源: Springer

【 摘 要 】

BackgroundMTHFD2 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.Materials and methodsThe 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.ResultsWe 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.ConclusionMTHFD2, 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.

【 授权许可】

CC BY