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Abstract Background New mechanistic insights into the self-renewal ability and multipotent properties of neural stem cells (NSCs) are currently under active investigation for potential use in the treatment of neurological diseases. In this study, NSCs were isolated from the forebrain of fetal rats and cultured to induce NSC differentiation, which was associated with low expression of the non-coding RNA microRNA-335-3p (miR-335-3p). Methods Loss- and gain-of-function experiments were performed in NSCs after induction of differentiation. Results Overexpression of miR-335-3p or FoxM1 and inhibition of the Fmr1 or p53 signaling pathways facilitated neurosphere formation, enhanced proliferation and cell cycle entry of NSCs, but restricted NSC differentiation. Mechanistically, FoxM1 positively regulated miR-335-3p by binding to its promoter region, while miR-335-3p targeted and negatively regulated Fmr1. Additionally, the promotive effect of miR-335-3p on NSC self-renewal occurred via p53 signaling pathway inactivation. Conclusion Taken together, miR-335-3p activated by FoxM1 could suppress NSC differentiation and promote NSC self-renewal by inactivating the p53 signaling pathway via Fmr1.

Abstract Background LncRNA was known to be closely associated with the progression of human tumors. The role of lncRNA LIFR-AS1 in the pathogenesis and progression of gastric tumor is still unclear. The aim of this study was to investigate the function of LIFR-AS1 and the underlying mechanism in the pathogenesis and progression of gastric cancer. Methods QRT-PCR was used to evaluate the expression of LIFR-AS1, miR-29a-3p and COL1A2 in gastric tumor tissues and cells. Western blotting was used to evaluate the protein expression of COL1A2 in gastric tumor cells. CCK-8 assay, transwell assay and flow cytometry were used to evaluate the roles of LIFR-AS1, miR-29a-3p and COL1A2 in cell proliferation, invasion, migration and apoptosis. The relationship among LIFR-AS1, miR-29a-3p and COL1A2 was assessed by bioinformatics analyses and luciferase reporter assay. Results The expression levels of LIFR-AS1 were significantly increased in gastric tumor tissues and cells, while the expression levels of miR-29a-3p were decreased. The expression of miR-29a-3p was negatively correlated with the expression of LIFR-AS1 in gastric cancer tumor tissues. Knocking down of LIFR-AS1 inhibited proliferation, invasion and migration of gastric tumor cells, and induced apoptosis of gastric tumor cells. Bioinformatics analyses and integrated experiments revealed that LIFR-AS1 elevated the expression of COL1A2 through sponging miR-29a-3p, which further resulted in the progression of gastric tumor. Conclusion LIFR-AS1 plays an important role as a competing endogenous RNA in gastric tumor pathogenesis and may be a potential target for the diagnosis and treatment of gastric tumor.

Abstract Background 17AAG has been extensively studied for its antitumor effects that protect cells from lethal stress by maintaining protein stability. The role of 17AAG in sevoflurane-induced neuronal injury has never been studied. We aim to investigate the effect of 17AAG on sevoflurane-induced neurotoxicity in vivo and in vitro. Methods Sevoflurane-induced hippocampal neuron injury model was established in aged Sprague–Dawley rats. Pretreatment of vehicle or 17AAG was administered prior to sevoflurane inhalation. H4 neuroglioma cells were pretreated with vehicle or 17AAG and exposed to sevoflurane. Apoptosis, oxidative stress, expression of interleukin-6 (IL-6), and activation of the nuclear factor-κB (NF-κB) signaling pathway in H4 cells were examined by Hoechst assay, flow cytometry, Western blot, and immunofluorescent staining. RNA interference against HSPA1A was performed to test the function of HSP70 in neuroprotection. Results Exogenous 17AAG reduced sevoflurane-induced apoptosis and oxidative stress in rat hippocampal neurons and in H4 cells. In H4 cells, 17AAG suppressed sevoflurane-induced upregulation of IL-6 and activation of NF-κB signaling. 17AAG enhanced sevoflurane-induced upregulation of HSP70 in rat hippocampal neurons and in H4 cells. Conversely, silencing of HSPA1A in H4 cells blocked the cytoprotective effect of 17AAG against sevoflurane-induced apoptosis and oxidative stress, and prevented upregulation of IL-6 and activation of NF-κB signaling. Conclusions 17AAG protects against sevoflurane-induced neurotoxicity in vivo and in vitro via HSP70-dependent inhibition of apoptosis, oxidative stress, and pro-inflammatory signaling pathway.