Hepatocellular carcinoma (HCC) typically relies on angiogenesis for its malignant behavior, including growth and metastasis. Vasohibin 2 (VASH2) was previously identified as an angiogenic factor, but its role in tumorigenesis is unknown. Using quantitative PCR and western blot analyses, we found that VASH2 is overexpressed in HCC cells and tissues. Using chromatin immunoprecipitation, we detected histone modifications at the putative VASH2 promoter, with increased H3K4 trimethylation and H3 acetylation and decreased H3K27 trimethylation, suggesting that epigenetic mechanisms are responsible for the deregulated VASH2 transcription in HCC. Knockdown of VASH2 via siRNA inhibited the proliferation of the hepatoma cell lines by delaying cell cycle progression and increasing apoptosis. Importantly, we found VASH2 secreted in the culture supernatant, and co-expression of its secretory chaperone small vasohibin-binding protein (SVBP) further enhanced VASH2 secretion. The supernatant from HepG2 cells expressing VASH2 enhanced the proliferation, migration and tube formation of human umbilical vein endothelial cells, and knockdown of VASH2 significantly inhibited these effects. In an in vivo study using a nude mouse model, we found that exogenous VASH2 significantly contributed to tumor growth, microvessel density and hemoglobin concentration in the tumors. Further analyses showed that the VASH2-mediated increase in the transcription of fibroblast growth factor-2, vascular endothelial growth factor and vasohibin 1 may be the mechanism underlying these effects. Taken together, these data indicate that VASH2 is abnormally expressed in HCC cells as a result of histone modifications and that VASH2 contributes to the angiogenesis in HCC via an SVBP-mediated paracrine mechanism. These results indicate a novel and important role for VASH2 in HCC angiogenesis and malignant transformation.
To investigate a possible association between miR-101 and apoptosis of human trophoblast cells mediated by endoplasmic reticulum protein 44 (ERp44) in preeclampsia (PE), we explored the expression of miR-101 in PE placentas (n=30) compared with normotensive pregnant placentas (n=30) and the correlation between miR-101 and ERp44 was also analyzed. Furthermore, both the apoptotic rate of trophoblast cells and the ER stress-induced apoptotic proteins were assayed when the HTR-8/SVneo cells were treated with miR-101 mimics or inhibitors in vitro. We found a lower expression of miR-101 and an inverse correlation between miR-101 and ERp44 protein in PE placentas. Upregulation of miR-101 expression could inhibit trophoblast HTR-8/SVneo cell apoptosis and repress ER stress-induced apoptotic proteins by targeting ERp44 in vitro, whereas inhibition of miR-101 could induce HTR-8/SVneo cell apoptosis. Our findings indicated that overexpression of miR-101 could downregulate ERp44 and suppress apoptosis in trophoblast cells during PE. Therefore, loss of miR-101 expression could contribute to ER stress-induced trophoblast cell apoptosis by targeting ERp44.
This study shows the ability of sodium-glucose co-transporter-2 inhibitors to lower atrial natriuretic peptide levels and improve glycaemic control, which may benefit the cardiovascular system.
research, the author found that GSTP1 promoter methylation rate was increased greatly in nonsurvived patients compared to those survived (54.71 vs. 7.08, P < 0.01). Aberrant GSTP1 promoter methylation might participate in the development and progression of ACHBLF, because the loss of GSTP1 gene expression might lead to the increase in cytotoxic molecules and liver cell damage. And the components of MELD score only reflect the consequence of liver injury. Therefore, GSTP1 promoter methylation rate might serve as a better predictive parameter for short-term mortality than MELD scores in early stage of ACHBLF. Besides all those excellent findings, there is a minor fault of that article. The author stated that 'In ACHBLF group, GSTP1 methylation level was significantly correlated with TBIL (Spearman's r = 0.29, P < 0.01), PTA (Spearman's r = À0.24, P = 0.01) and MELD score (Spearman's r = 0.26, P = 0.01)'. Although achieving values of P < 0.05, it does not indicate the strength of the Spearman rank-order correlation. In fact, an r value between 0.00 and 0.30 (or 0.00 to À0.030) usually means negligible correlation.9 Therefore, it is inaccurate to draw the conclusion that GSTP1 methylation rate is correlated with TBIL, PTA or MELD score. Nevertheless, Gao et al. have carried out meaningful work in the area of liver failure. The invalidation of GSTP1 methylation for predicting the outcome of acute-on-chronic hepatitis B liver failure or other causes of liver failure is worthy of further investigation. ACKNOWLEDGEMENTDeclaration of personal and funding interests: None.
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