The role of interleukin-17 in epilepsy.

Epilepsy is a common neurological disorder that seriously affects human health. It is a chronic central nervous system dysfunction caused by abnormal discharges of neurons. About 50 million patients worldwide are affected by epilepsy. Although epileptic symptoms of most patients are controllable, some patients with refractory epilepsy have no response to antiseizure medications. It is necessary to investigate the pathogenesis of epilepsy and identify new therapeutic targets for refractory epilepsy. Epileptic disorders often accompany cerebral inflammatory reactions. Recently, the role of inflammation in the onset of epilepsy has increasingly attracted attention. The activation of both innate and adaptive immunity plays a significant role in refractory epilepsy. According to several clinical studies, interleukin-17, an essential inflammatory mediator linking innate and adaptive immunity, increased significantly in the body liquid and epileptic focus of patients with epilepsy. Experimental studies also indicated that interleukin-17 participated in epileptogenesis through various mechanisms. This review summarized the current studies about interleukin-17 in epilepsy and aimed at finding new therapeutic targets for refractory epilepsy.

LncRNA SNHG6 promotes LMO3 expression by sponging miR-543 in glioma.

Small nucleolar RNA host gene 6 (SNHG6) was a newly discovered long non-coding RNA, which was involved in the occurrence and development of a variety of cancers and was on the rise in human cancers. However, the molecular mechanism of SNHG6 in glioma required further investigation. The levels of SNHG6, microRNA-543 (miR-543) and LIM-only protein 3 (LMO3) were detected in glioma tissues and cells by quantitative real-time polymerase chain reaction. We examined cell proliferation and apoptosis rate by methylthiazolyldiphenyl-tetrazolium bromide and flow cytometry assays, respectively. Transwell assay was used to measure cell migration and invasion. The target relationships were predicted by StarBase v.2.0 and TargetScan and confirmed by dual-luciferase reporter assay. Spearman's test was adopted for expression correlation of SNHG6, miR-543 and LMO3 in tissues. The protein expression level of LMO3 was assessed by western blot. We found that SNHG6 was obviously upregulated in glioma tissues and cells. SNHG6 knockdown significantly repressed glioma cell proliferation, migration and invasion, and induced apoptosis. Additionally, SNHG6 directly targeted miR-543 and their expression was negatively correlated in glioma tissues. And miR-543 targeted LMO3 and their expression was also inversely correlated. We found that silencing LMO3 also inhibited the progression of glioma cells. Importantly, SNHG6 could competitively sponging miR-543 thereby modulating LMO3 in glioma cells. SNHG6 served as an oncogene and played a vital role in glioma development through miR-543/LMO3 axis.

Lactate dehydrogenase A promotes the invasion and proliferation of pituitary adenoma.

Lactate dehydrogenase A (LDHA) has been reported to be involved in the initiation and progression of tumors. However, the potential role of LDHA in pituitary adenoma (PA) remains unknown. In this study, we showed that the expression levels of LDHA mRNA and protein were significantly elevated in invasive PA samples, and positively correlated with higher Ki-67 index. Overexpression of LDHA in a PA cell line (GH3) promoted glucose uptake through the upregulation of glucose transporter-1 (Glut1), lactate secretion and induced cellular invasion by upregulation of matrix metalloproteinase2 (MMP2). LDHA also promoted GH3 cell proliferation through induction of cell cycle progression via activation of the Akt-GSK-3ß-cyclinD1 pathway. Accordingly, oxamate-induced inhibition of LDHA suppressed glucose uptake, lactate secretion, invasion and proliferation in GH3 cells via down regulation of Glut1 and MMP2 expression and inhibition of the Akt-GSK-3ß-cyclinD1 pathway. Moreover, oxamate induced GH3 cell apoptosis by increasing mitochondrial reactive oxygen species (ROS) generation. In vivo, LDHA overexpression promoted tumor growth, and oxamate delayed tumor growth. In primary PA cell cultures, oxamate also effectively suppressed invasion and proliferation. Our data indicate that LDHA is involved in promoting the progression of PA, and oxamate might be a promising therapeutic agent for the treatment of PA.

Metformin inhibits proliferation and growth hormone secretion of GH3 pituitary adenoma cells.

Metformin is an anti-hyperglycemic agent used to treat diabetes, and recent evidence suggests it has antitumor efficacy. Because growth hormone-secreting pituitary adenoma (GH-PA) patients have a high incidence of diabetes frequently treated with metformin, we assessed the antitumor effect of metformin on GH-PA. We found that metformin effectively inhibited proliferation and induced apoptosis in the GH-PA cell line GH3. We detected a decrease in mitochondrial membrane potential (MMP), an increase in expression of pro-apoptotic proteins, and a decrease in expression of an anti-apoptotic protein in metformin-treated GH3 cells, which suggests involvement of the mitochondrial-mediated apoptosis pathway. Inhibition of AMPK, which is activated by metformin, failed to reverse the antiproliferative effect. ATF3 was upregulated by metformin, and its knockdown significantly reduced metformin-induced apoptosis. In addition, GH secretion was inhibited by metformin through suppression of STAT3 activity independently of AMPK. Metformin also significantly suppressed cellular proliferation and GH secretion in primary human GH-PA cells. Metformin also significantly inhibited GH3 cell proliferation and GH secretion in vivo. ATF3 upregulation and p-STAT3 downregulation were confirmed in xenografts. These findings suggest metformin is a potentially promising therapeutic agent for the treatment of GH-PA, particularly in patients with diabetes.

Evidence for possible role of toll-like receptor 3 mediating virus-induced progression of pituitary adenomas.

Tumor-related viruses are known to be involved in initiation and progression of certain tumors. However, the relationship between virus and pituitary adenomas (PAs) remains unknown. Here, we investigated infection status of three types of viruses (HPV16, HHV6B and HSV1) and expression level of toll-like receptor 3 (TLR3) in 60 human PA samples. We also determined the role of TLR3 signaling pathway on a PA cell line (GH3). We firstly found that positive rates of HPV16 and HHV6B infection were significantly higher in invasive PA samples than in noninvasive samples (P < 0.01). Similarly, TLR3 mRNA and protein expression also increased in invasive PA samples (P < 0.01). In vitro analysis indicated that GH3 cell proliferation and survival were enhanced by TLR3 activation, which was accompanied by NF-κB activation. Our data indicate that HPV16 and HHV6B viruses may be involved in promoting the progression of PA by activating the TLR3 signaling pathway.