Down‐regulation of MTHFD2 inhibits NSCLC progression by suppressing cycle‐related genes

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. K E Y W O R D S bioinformatics, cell cycle, methylenetetrahydrofolate dehydrogenase 2, non-small cell lung cancer | 1569 YU et al. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Yu C, Yang L, Cai M, et al. Downregulation of MTHFD2 inhibits NSCLC progression by suppressing cycle-related genes. J Cell Mol Med.

Identification of candidate biomarkers associated with the diagnosis and prognosis of endometrial cancer: a bioinformatics analysis

“…MTHFD2 overexpression is associated with poor prognosis and tumor metastasis in HCC and breast cancer [24,25]. In vitro and in vivo experiments of NSCLC indicated that knockdown of MTHFD2 can reduce cell growth and tumorigenicity [26]. Kawai et al [27] reported that DS18561882, an MTHFD2 inhibitor, has a strong antitumor effect on mouse xenograft model.…”

MTHFD2 facilitates breast cancer cell proliferation via the AKT signaling pathway

“…It was demonstrated that suppression of MTHFD2 inhibits methylation reactions (7), decreases protein synthesis (9) and disrupts redox homeostasis (6,10), which may ultimately result in significant changes in cellular metabolic phenotype. Because MTHFD2 expression was reported as a key participant in the metabolic reprogramming in tumors (7) and a predictive factor of poor prognosis in patients with various types of cancer (8,(11)(12)(13), including breast cancer (14), MTHFD2 has received increased attention recently and might be considered as a potential anticancer target. Numerous studies have also demonstrated a strong association between tumor cell phenotype and MTHFD2 expression status (13,15,16).…”

Up-regulated Expression of MTHFD2 Correlates with Favorable Prognosis in LGG Patients: A Bioinformatic Analysis

“…MTHFD2 was found highly expressed in colorectal cancer (CRC) cells, and silence of MTHFD2 expression inhibited the proliferation, weakened the migration ability and promoted the apoptosis of CRC cells [17]. MTHFD2 was also significantly over-expressed in non-small cell lung cancer (NSCLC) tissues, and knockdown of MTHFD2 resulted in reduction of tumor cell growth and tumorigenicity [18]. In addition, MTHFD2 over-expression was associated with cell proliferation and vimentin-modulated migration and invasion in renal cell carcinoma (RCC) [19].…”