Overexpression of Mitochondrial Serine Hydroxyl-methyltransferase 2 is Associated with Poor Prognosis and Promotes Cell Proliferation and Invasion in Gliomas

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2017 Aug 11

PMID 28794642

Citations 20

Authors

Ming Wu

Siyi Wanggou

Xuejun Li

Qing Liu

Yuanyang Xie

Affiliations

Soon will be listed here.

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 (<0.001). In addition, SHMT2 overexpression more frequently occurred in glioma patients with an advanced grade of malignancy (<0.001) and poor prognosis (=0.001). Notably, multivariate analysis based on a Cox regression model identified SHMT2 expression as an independent prognostic factor for glioma patients (=0.01). Functionally, SHMT2 knockdown efficiently suppressed the proliferation (=0.02) and invasion (<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.

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