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BackgroundHepatocellular carcinoma (HCC) is the most major type of primary hepatic cancer. Serine hydroxymethyltransferase 1 (SHMT1) is recently found to play critical roles in human cancers including lung cancer, ovarian cancer and intestinal cancer. However, the expression, function and the underlying mechanisms of SHMT1 in HCC remain uncovered.MethodsqRT-PCR, immunohistochemistry and immunoblotting were performed to detect the expression of SHMT1 in HCC tissues and cell lines. HCC cell migration and invasion were determined by Boyden chamber and Transwell assay in vitro, and tumor metastasis was assessed via lung metastasis model in mice. The expression of key factors involved in epithelial-to-mesenchymal transition (EMT) process was evaluated by western blotting.ResultsIn this study, data mining of public databases and analysis of clinical specimens demonstrated that SHMT1 expression was decreased in HCC. Reduced SHMT1 level was correlated with unfavorable clinicopathological features and poor prognosis of HCC patients. Gain- and loss-of-function experiments showed that SHMT1 overexpression inhibited the migration and invasion of HCCLM3 cells while SHMT1 knockdown enhanced the metastatic ability of Hep3B cells. Furthermore, qRT-PCR and western blotting showed that SHMT1 inhibited EMT and matrix metallopeptidase 2 (MMP2) expression. In vivo experiments showed that SHMT1 suppressed the lung metastasis of HCC cells in mice. Mechanistically, SHMT1 knockdown enhanced reactive oxygen species (ROS) production, and thus promoted the motility, EMT and MMP2 expression in Hep3B cells. Furthermore, NADPH oxidase 1 (NOX1) was identified to be the downstream target of SHMT1 in HCC. NOX1 expression was negatively correlated with SHMT1 expression in HCC. Rescue experiments revealed that NOX1 mediated the functional influence of SHMT1 on HCC cells.ConclusionsThese data indicate that SHMT1 inhibits the metastasis of HCC by repressing NOX1 mediated ROS production.Electronic supplementary materialThe online version of this article (10.1186/s13046-019-1067-5) contains supplementary material, which is available to authorized users.

The phosphorescence spectrum of vanadium oxide anchored onto Si02 shows well-resolved vibrational fine structure at 77 K. Franck-Condon analysis of the phosphorescence indicates that the internuclear equilibrium distance between oxygen and vanadium ions of V=0 vanadyl groups as emitting sites of V/Si02 catalyst anchored onto Si02 is larger by 0.12 A in its charge-transfer excited triplet state than in its ground state. UV irradiation of the catalyst in the presence of CO leads to the formation of C02 (photoreduction of the catalyst) and adsorption of CO. In this former photoreaction, a good linear relationship between the yields of photoformed C02 and the yields of phosphorescence is observed. Since photoformation of C02 is accompanied by the removal of oxygen from the catalyst, both theoretical Franck-Condon analysis and experimental results indicate not only that the charge-transfer excited state of the surface vanadyl group of the catalyst plays a significant role in the photoreaction but also that an elongation of the internuclear distance between vanadium and oxygen ions in the excited state of the vanadyl groups may be associated with the easier photoreduction of the catalyst with CO.

Visible light induced photoredox catalysis is an efficient method for radical activation. Herein, we report the photoredox catalysis involving an intramolecular radical-radical coupling reaction that proceeds through a biradical intermediate. This protocol represents a new synthetic route to construct multi-substituted N-heterocycles. Four, five and six-membered N-heterocyclic structures with a quaternary carbon center are accessible under mild conditions.