SIRT7 knockdown promotes gemcitabine sensitivity of pancreatic cancer cell via upregulation of GLUT3 expression.

Gemcitabine serves as a first-line chemotherapeutic treatment for pancreatic cancer (PC), but it is prone to rapid drug resistance. Increasing the sensitivity of PC to gemcitabine has long been a focus of research. Fasting interventions may augment the effects of chemotherapy and present new options. SIRT7 is known to link metabolism with various cellular processes through post-translational modifications. We found upregulation of SIRT7 in PC cells is associated with poor prognosis and gemcitabine resistance. Cross-analysis of RNA-seq and ATAC-seq data suggested that GLUT3 might be a downstream target gene of SIRT7. Subsequent investigations demonstrated that SIRT7 directly interacts with the enhancer region of GLUT3 to desuccinylate H3K122. Our group's another study revealed that GLUT3 can transport gemcitabine in breast cancer cells. Here, we found GLUT3 KD reduces the sensitivity of PC cells to gemcitabine, and SIRT7 KD-associated gemcitabine-sensitizing could be reversed by GLUT3 KD. While fasting mimicking induced upregulation of SIRT7 expression in PC cells, knocking down SIRT7 enhanced sensitivity to gemcitabine through upregulating GLUT3 expression. We further confirmed the effect of SIRT7 deficiency on the sensitivity of gemcitabine under fasting conditions using a mouse xenograft model. In summary, our study demonstrates that SIRT7 can regulate GLUT3 expression by binding to its enhancer and altering H3K122 succinylation levels, thus affecting gemcitabine sensitivity in PC cells. Additionally, combining SIRT7 knockdown with fasting may improve the efficacy of gemcitabine. This unveils a novel mechanism by which SIRT7 influences gemcitabine sensitivity in PC and offer innovative strategies for clinical combination therapy with gemcitabine.

Facile Preparation of Ultrathin Co3 O4 /Nanocarbon Composites with Greatly Improved Surface Activity as a Highly Efficient Oxygen Evolution Reaction Catalyst.

The efficient catalytic oxidation of water to dioxygen plays a significant role in solar fuel and artificial photosynthetic systems. It remains highly challenging to develop oxygen evolution reaction (OER) catalysts with high activity and low cost under mild conditions. Here, a new composite material is reported based on ultrathin 2D Co3 O4 nanosheets and reduced graphene oxides (rGO) by means of a one-pot hydrothermal strategy. The ultrathin Co3 O4 /rGO nanocomposite shows superior stability under alkaline conditions and exhibits an overpotential of 290 mV with a Tafel slope of 68 mA dec-1 , which is much smaller than that of bare Co3 O4 catalyst. Extensive experiments were also carried out using 0D CS and 1D CNTs (CS=carbon spheres, CNTs=carbon nanotubes) in place of the 2D rGO. The overpotentials of as-prepared nanocomposites decrease with the increase of the dimension of nanocarbons, suggesting the electrochemistry activity is closely related to the surface area of carbon substrates. In addition, compared with ultrathin 2D Co3 O4 nanosheets with a Co2+ /Co3+ ratio of 1.2, the as-prepared ultrathin Co3 O4 /rGO nanocomposite with a Co2+ /Co3+ ratio of 1.4 contributes to the better OER performance as more oxygen vacancies can be formed in the ultrathin Co3 O4 /rGO nanocomposite under the experimental conditions. Compared with other Co3 O4 -containing composite materials reported so far, the ultrathin Co3 O4 /rGO nanocomposites show excellent OER performance.