Overexpression of mitochondrial serine hydroxyl-methyltransferase 2 is associated with poor prognosis and promotes cell proliferation and invasion in gliomas

Abstract

Mitochondrial serine hydroxyl-methyltransferase 2 (SHMT2), participating in the synthesis of mitochondrial thymidine monophosphate, has been reported to drive glioma cell survival in ischemia. However, its clinical relevance in gliomas remains unclear. In the current study, immunohistochemistry was performed to examine subcellular localization and expression levels of SHMT2 protein in glioma and non-neoplastic brain tissue specimens. Then, the associations of SHMT2 expression with various clinicopathological features and patients’ prognosis were statistically evaluated. The roles of SHMT2 in the proliferation and invasion of glioma cells after siRNA-SHMT2 vector transfection were also detected by cell counting kit-8 and transwell assays, respectively. Results showed that SHMT2 immunostaining was predominantly localized in the cellular cytoplasm of tumor cells in glioma tissues but weakly in non-neoplastic brain tissues. Statistically, SHMT2 protein expression was significantly higher in glioma tissues than in non-neoplastic brain tissues (P<0.001). In addition, SHMT2 overexpression more frequently occurred in glioma patients with an advanced grade of malignancy (P<0.001) and poor prognosis (P=0.001). Notably, multivariate analysis based on a Cox regression model identified SHMT2 expression as an independent prognostic factor for glioma patients (P=0.01). Functionally, SHMT2 knockdown efficiently suppressed the proliferation (P=0.02) and invasion (P<0.001) of glioma cells in vitro. In conclusion, our findings suggest that SHMT2 may function as an oncogene in glioma development and progression. Clinically, SHMT2 may serve as a prognostic factor and as a potential therapeutic target for human gliomas.

Chloroplastic Serine Hydroxymethyltransferase From Medicago truncatula: A Structural Characterization

“…The one-carbon units result mainly from the activity of serine hydroxymethyltransferases (SHMTs, EC 2.1.2.1), which reversibly interconvert Ser and glycine (Gly). Consistently, an increasing amount of evidence has pinpointed SHMTs as pivotal in highly proliferating cells ( Girgis et al, 1997 ; Townsend et al, 2004 ; Wu et al, 2017 ).…”

TMPRSS2 Correlated With Immune Infiltration Serves as a Prognostic Biomarker in Prostatic Adenocarcinoma: Implication for the COVID-2019

“…At the same time, studies have found that TMPRSS2 cells are a useful experimental system for studying the cleavage and inhibition of HA by host cell proteases. In addition, these cells also represent a suitable cell line for propagation of the influenza virus in the absence of trypsin (Wu et al, 2017). Interestingly, TMPRSS2 can cleave SARS-COV-2 spike protein, thus facilitating viral entry and activation (Hoffmann et al, 2020), which suggest its correlation with SARS-COV-2.…”

Silencing SHMT2&nbsp;Inhibits the Progression of Oral Squamous Cell Carcinoma Through Cell Cycle Regulation

“…SHMT2, located on human chromosome 17, is responsible for encoding the mitochondrial form of a pyridoxal phosphate-dependent enzyme [13]. An important paralog of SHMT is SHMT1, which is mainly present in the cytoplasm [14].…”

“…An important paralog of SHMT is SHMT1, which is mainly present in the cytoplasm [14]. SHMT2 is primarily involved in catalyzing the conversion of serine to glycine, and simultaneously transfers b-carbon from serine to hydrolyzed tetrahydro ate (THF) to form 5,10-methylenettrahydrofolate (Me THF) [13,15]. As the hub of serine catabolism and single carbon metabolism, SHMT2 plays a regulatory role, in which small molecular metabolites control cell proliferation [16].…”