Serine hydroxymethyltransferase 1 promotes low-grade glioma progression by activating mTORC1 signaling
Ye Gao, Nianliang Jing, Xukun Teng, Yong Wang
Abstract
OBJECTIVES: This research aimed to explore the role and potential mechanism of serine hydroxymethyltransferase 1 (SHMT1) involvement in low-grade glioma (LGG). METHODS: GEPIA were employed to analyze the expression and the correlation of LGG patient survival with the levels of SHMT1 in LGG based on the The Cancer Genome Atlas (TCGA) database. qRT-PCR and western blot were used to detect the expression of SHMT1 in LGG cells. Clone formation, EdU staining, MTT, Transwell and wound healing assays were conducted to analyze the proliferation, cell activity, migration and invasion of LGG cells. KEEG analysis was performed for enrichment pathways of SHMT1 in LGG. RESULTS: SHMT1 was up-regulated in LGG tissues and cells, and SHMT1 level was negatively correlated with survival of patients with LGG. SHMT1 overexpression evidently promoted cell proliferation, migration and invasion, whereas SHMT1 silence obtained the opposite results. Next, KEEG analysis revealed that SHMT1 activated the mTORC1 pathway in LGG. SHMT1 overexpression significantly promoted the phosphorylation of downstream proteins (P70SK6 and S6) in LGG cells. Further, inhibition of the mTORC1 signaling pathway partially abolished the promotion of LGG progression by SHMT1 overexpression. CONCLUSION: SHMT1 promoted proliferation, invasion and migration of LGG cells via activating mTORC1 signaling pathway. This provided a novel perspective for the treatment of LGG.