MicroRNA-33a-5p suppresses colorectal cancer cell growth by inhibiting MTHFD2.

Colorectal cancer (CRC) is one of the most common malignancies with high levels of invasiveness, drug resistance and mortality, but the internal mechanisms of CRC are largely unknown. MicroRNAs (miRs) have been reported to be involved in the development of CRC, and numerous studies have demonstrated that the abnormal expression of miR-33a-5p might be associated with CRC. However, the function and downstream mechanism of miR-33a-5p in colorectal cancer (CRC) remains unclear. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial enzyme involved in folic acid metabolism, interestingly was confirmed to be one of the target genes of miR-33a-5p in the present study. We first confirmed that miR-33a-5p in CRC tissues and cell lines were downregulated (P < 0.05), and that the proliferation, clone formation capacities, G1/S progression, and migration capacities of the two CRC cell lines HCT116 cells and HT29 were suppressed by miR-33a-5p overexpression in vitro (P < 0.05). Ctrl HCT116 and miR-33a-5p-overexpressing HCT116 were injected into nude mice. In vivo tumour formation was significantly suppressed by miR-33a-5p overexpression (P < 0.05) as well as the proliferation marker Ki67 (P < 0.05). Additionally, MTHFD2 protein expression was significantly enhanced in CRC tissues. From bioinformatics predictions and a luciferase report analysis, MTHFD2 was confirmed to be one of the target genes of miR-33a-5p. In contrast to the role of miR-33a-5p overexpression, MTHFD2 overexpression promoted the proliferation and migration of HCT116 and HT29 cells (P < 0.05), which confirmed that MTHFD2 was a functional target gene of miR-33a-5p. In conclusion, miR-33a-5p inhibits the growth and migration of CRC by targeting MTHFD2.

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