Serine hydroxymethyltransferase 1 promotes low-grade glioma progression by activating mTORC1 signaling

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.

KEYWORDS:

• Low-grade glioma
• serine hydroxymethyltransferase 1
• proliferation
• mammalian target of rapamycin complex 1

Acknowledgments

The authors gratefully acknowledge all individuals who participated in this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Availability of data and material

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Ethics approval

No animal and patients

Authors’ contributions

Conception and design: Ye Gao; Perform research: Nianliang Jing and Xukun Teng; Data analysis and interpretation: Yong Wang; Manuscript writing: All authors; Final approval of manuscript: All authors

Additional information

Funding

The study was supported by Jinan Municipal Health Commission (Project Number: 2020-4-177). The project name: Correlation between cerebrospinal fluid and tumor gene sequences in high-grade glioma detected by next-generation sequencing technology.