MTHFD1L as a folate cycle enzyme correlates with prognostic outcome and its knockdown impairs cell invasive behaviors in osteosarcoma via mediating the AKT/mTOR pathway

Abstract

Osteosarcoma (OS) is the most frequent primary malignancy initially in bone with multiple genomic aberrations. Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) is linked with the progression of diverse tumors. However, its function in OS is not understood completely. The expression pattern and prognostic significance of MTHFD1L in OS tissues were analyzed based on GEO database. The expression level of MTHFD1L in OS cell lines was explored by qRT-PCR. The cell proliferation, colony formation ability, invasion as well as migration in OS cells after MTHFD1L knockdown were determined using cell counting kit 8 (CCK-8) assay, colony formation and transwell methods. GSEA analysis was performed to predict the underlying mechanisms of MTHFD1L in OS development. Furthermore, the western blot was utilized to study the influence of MTHFD1L on AKT/mTOR pathway. Our results indicated that MTHFD1L expression was significantly up-regulated in OS tissues and cells compared with normal tissues and cells. High expression of MTHFD1L could lead to poor prognosis of OS patients. Cell proliferation, colony formation ability, migration and invasion were blocked because of reduced MTHFD1L in vitro. Moreover, cell cycle and AKT/mTOR pathway were all associated with MTHFD1L expression. In conclusion, the findings revealed that MTHFD1L might promote the development of OS via mediating cell cycle and AKT/mTOR pathway, indicating that MTHFD1L might act as a promising therapeutic target for OS treatment.

Keywords:

• Osteosarcoma
• MTHFD1L
• prognosis
• cell cycle
• AKT/mTOR pathway

Disclosure statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.