Methylenetetrahydrofolate dehydrogenase 2 overexpression is associated with tumor aggressiveness and poor prognosis in hepatocellular carcinoma

Background: Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is the key enzyme in the transformation of folic acid metabolites. MTHFD2 overexpression plays a key role in the progression of human cancers, and depletion of MTHFD2 has shown potential antitumor activities in several types of cancer. However, the role of MTHFD2 in hepatocellular carcinoma (HCC) has not been investigated. Aims: To investigate the expression of MTHFD2 in HCC patients, and its associated clinical implications and possible functions in HCC. Methods: Reverse transcription-polymerase chain reaction and immunohistochemical staining were used to detect MTHFD2 expression in liver tissues from HCC patients, then associations of MTHFD2 expression with demographic and clinicopathologic features were analysed. The effects of siRNA interference of MTHFD2 on cell proliferation, cell cycle, apoptosis, and migration were investigated in HCC cell lines. Results: Significant overexpression of MTHFD2 was observed in HCC tissues, and overexpression of MTHFD2 was correlated with TNM stage, tumor microembolus, tumor metastasis, recurrence and the time of recurrence (P<0.05) in HCC patients. siRNA-mediated silencing of MTHFD2 inhibited migration, invasion and epithelial-mesenchymal transition progression in HCC cell lines, but no obvious effects on cell proliferation, apoptosis or cell cycle distribution were detected. Conclusions: MTHFD2 is overexpressed in HCC, and is associated with poor prognosis and cellular features connected to metastatic disease. (C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.