Dengfeng Ge

Glioma is a common and aggressive primary malignant brain tumor. However, the progression mechanism of glioma has not been well revealed. In this study, we intend to detect the function and related mechanism of STC2 in glioma. Gene Expression Profiling Interactive Analysis database was used to detect STC2 and ITGB2 expression in glioma samples, as well as the relationship between STC2 and other genes. The relationship between STC2 and ITGB2 was confirmed by co-immunoprecipitation assay. The biology function of glioma cells was determined by cell counting kit-8, colony formation, transwell, ELISA and western blot assays. We discovered that STC2 was highly expressed in glioma samples and cell lines. Knocked down of STC2 inhibited cell proliferation, invasion, migration and glycolysis. Further analysis demonstrated the interaction between ITGB2 and STC2 as well as its involvement in STC2-regulated proliferation, invasion, migration and glycolysis. In summary, our data afforded novel insights into understanding the regulatory mechanism of STC2 and suggested that the STC2/ITGB2 axis might be a potential therapeutic target for glioma. Graphical Abstract

Rotenone has recently been widely used to establish Parkinson’s disease (PD) models to replicate the features of PD. However, the mechanisms involved in rotenone neurotoxicity have not been elucidated. The aim of the present study was to identify the neurotoxicity of rotenone through intraperitoneal injection in mice and to investigate the global changes of phosphorylation proteomic profiles in rotenone-injured SH-SY5Y cells through a label-free proteomic analysis using a PTMScan with LC–MS/MS. ICR (Institute of Cancer Research) mice were intraperitoneally injected with different dosages of rotenone (1 mg/kg/d or 3 mg/kg/d) daily for 21 consecutive days. Rotenone caused a dose-dependent decrease in locomotor activities and a decrease in the number of Nissl-positive and tyrosine hydroxylase (TH)-immunoreactive neurons in the substantia nigra pars compacta (SNpc). Here, 194 phosphopeptides on 174 proteins were detected in SH-SY5Y cells, and 37 phosphosites on 33 proteins displayed statistically significant changes in expression after rotenone injury. The downregulation of phosphorylated Akt and mTOR was further confirmed by western blot analysis. A specific Akt activator, SC79, could protect cell viability and induce autophagy in rotenone-injured SH-SY5Y cells. This study indicates the involvement of the Akt/mTOR (mammalian target of rapamycin) signaling pathway in rotenone-injured SH-SY5Y cells and provides molecular information for the neurotoxicity of rotenone.