MTHFD1L knockdown diminished cells growth in papillary thyroid cancer

Abstract

Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 like (MTHFD1L) is a mitochondrial enzyme involved in the synthesis of tetrahydrofolate (THF). This study aimed to investigate the effect of MTHFD1L in papillary thyroid cancer (PTC). Tumor tissues and adjacent tissues from 11 patients with PTC were collected, the expression level of MTHFD1L mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The cancer genome atlas (TCGA) database was used for analysis MTHFD1L differentially expressed between tumor tissue and adjacent tissues. MTHFD1L was knocked down by a lentivirus-based system and CRISPR-Cas9. Affymetrix genechip human transcriptome array 2.0 was used to assess gene expression. Cell growth and motility were evaluated in vivo and in vitro. Cell apoptosis and cell cycle were investigated by flow cytometry assay. The expression levels of proteins were detected by western blotting. MTHFD1L mRNA and protein expression levels significantly increased in tumor tissues and CAL-62, K1 and TPC-1 cell lines. After knockdown MTHFD1L, the growth of cells were reduced while cell apoptosis was increased. In addition, tumor growth was inhibited after MTHFD1L knockdown in nude mice. Affymetrix genechip human transcriptome array 2.0 was founded that MTHFD1L knockdown can inhibit the expression levels of CCND1 and Notch2. Furthermore, we identified that MTHFD1L knockdown inhibited cells growth and induced cell apoptosis in PTC. Importantly, MTHFD1L knockdown decreased the expression levels of Notch2, Hes1 CCND1, Bcl-2, and PCNA protein, whereas the level of Bax increased. Our study suggested MTHFD1L knockdown could diminished PTC cell proliferation. MTHFD1L serves as a valuable therapeutic target.