BackgroundThe signal transducer and activator of transcription (STAT) and transforming growth factor-β (TGF-β) signaling pathways play important roles in epithelial ovarian cancer (EOC). However, the mechanism of crosstalk between two pathways is not completely understood.MethodsThe expression of STAT1 protein was detected by tissue microarray and immunoblotting (IB). The interaction of STAT1 isoforms with TGF-β receptors was confirmed by immunoprecipitation and IB. The effect of TGF-β signaling on STAT1 activation was examined in EOC and non-tumorous HOSEpiC cells treated with TGF-β1 in the presence or absence of the inhibitor of TGF-β type I receptor. The gain-of-function and loss-of-function approaches were applied for detecting the role of STAT1 on EOC cell behaviours.ResultsThe high level of STAT1 was observed in patients with high-grade serous EOC. STAT1 expression was higher in ovarian cancer cells than noncancerous cells. TGF-β1 activated the STAT1 pathway by inducing the phosphorylation of STAT1α on S727 residue. The full-length STAT1α and the truncated STAT1β directly interacted with TGF-β receptors (ALK1/ALK5 and TβRII), which was mediated by TGF-β1. STAT1α and STAT1β blocked the activation of the TGF-β1 signaling pathway in EOC cells by reducing Smad2 phosphorylation. STAT1 overexpression induced EOC cell proliferation, migration, and invasion; whereas its inhibition enhanced TGF-β1-induced phospho-Smad2 and suppressed EOC cell proliferation, migration, and invasion.ConclusionsOur data unveil a novel insight into the molecular mechanism of crosstalk between the STAT1 and TGF-β signaling pathways, which affected the cancer cell behavior. Suppression of STAT1 may be a potential therapeutic strategy for targeting ovarian cancer.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0773-8) contains supplementary material, which is available to authorized users.

Stroke is a neurological disease with high disability and fatality rates, and ischemic stroke accounts for 75% of all stroke cases. The underlying pathophysiologic processes of ischemic stroke include oxidative stress, toxicity of excitatory amino acids, excess calcium ions, increased apoptosis and inflammation. Long non-coding RNAs (lncRNAs) may participate in the regulation of the pathophysiologic processes of ischemic stroke as indicated by altered expression of lncRNAs in blood samples of acute ischemic stroke patients, animal models of focal cerebral ischemia and oxygen-glucose deprivation (OGD) cell models. Because of the potentially important role, lncRNAs might be useful as biomarkers for the diagnosis, treatment and prognosis of ischemic stroke. This article reviews the functions of lncRNAs in different pathophysiology events of ischemic stroke with a focus on specific lncRNAs that may underlie ischemic stroke pathophysiology and that could therefore serve as potential diagnostic biomarkers and therapeutic targets.

Pyridoxine 5′-phosphate oxidase (PNPO) is an enzyme that converts pyridoxine 5′-phosphate into pyridoxal 5′-phosphate (PLP), an active form of vitamin B6 implicated in several types of cancer. However, the role of PNPO and its regulatory mechanism in epithelial ovarian cancer (EOC) are unknown. In the present study, PNPO expression in human ovarian tumour tissue and its association with the clinicopathological features of patients with EOC were examined. Further, the biological function of PNPO in EOC cells and in xenograft was evaluated. We demonstrated for the first time that PNPO was overexpressed in human EOC. Knockdown of PNPO induced EOC cell apoptosis, arrested cell cycle at G2/M phase, decreased cell proliferation, migration and invasion. Xenografts of PNPO-shRNA-expressing cells into the nude mouse attenuated tumour growth. PNPO at mRNA and protein levels in EOC cells was decreased after transforming growth factor-β1 (TGF-β1) treatment. The inhibitory effect of TGF-β1 on PNPO expression was abolished in the presence of SB-431542, a TGF-β type I receptor kinase inhibitor. Moreover, we found that TGF-β1-mediated PNPO expression was at least in part through the upregulation of miR-143-3p. These data indicate a mechanism underlying PNPO regulation by the TGF-β signalling pathway. Furthermore, PLP administration reduced PNPO expression and decreased EOC cell proliferation, suggesting a feedback loop between PLP and PNPO. Thus, our findings reveal that PNPO can serve as a novel tissue biomarker of EOC and may be a potential target for therapeutic intervention.

The miR-200 family was recently identified as a suppressor of epithelial-mesenchymal transition (EMT). The loss or gain of miR-200 family members is associated with cancer invasion. The epidermal growth factor receptor (EGFR) is overexpressed in the majority of anaplastic thyroid cancers (ATCs). The activation of EGFR by its ligand, epidermal growth factor (EGF), activates a signaling cascade that results in the enhanced migration and invasiveness of thyroid cancer cells. However, little is known about the potential interrelationships between EGF/EGFR, miR-200s and the induction of EMT or mesenchymal-epithelial transition (MET) processes. This study aimed to investigate the regulatory role of miR-200s in EMT modulation by EGF/EGFR. Using transfection, real-time reverse transcription PCR and western blot analysis, we found that the EGF treatment of Nthy-ori 3-1 thyroid follicular cells resulted in the downregulation of E-cadherin and the upregulation of vimentin. By contrast, EGFR silencing in SW1736 human thyroid carcinoma cells led to the upregulation of E-cadherin and the downregulation of vimentin. In addition, EGF signaling correlated with the reduced expression of miR-200s and the re-expression of miR-200s abrogated the effects of EGF treatment and restored an epithelial phenotype to EGF-induced Nthy-ori 3-1 cells. Conversely, the silencing of miR-200s in SW1736 cells overcame siEGFR-induced changes in gene expression and phenotype. In addition, we demonstrate that miR-200s play a key role in in vitro EGF/EGFR-mediated thyroid cell invasion and in EMT in vivo. We, therefore, provide a mechanistic link between the miR-200 family and EGF/EGFR, which suggests that miR-200 upregulation may serve as a novel therapeutic strategy for highly invasive thyroid cancers.