GDPD5 Related to Lipid Metabolism Is a Potential Prognostic Biomarker in Neuroblastoma.

Neuroblastoma (NB) is an extracranial solid tumor in children with poor prognosis in high-risk patients and its pathogenesis and prognostic markers urgently need to be explored. This study aimed to explore potential biomarkers related to NB from the aspect of lipid metabolism. Fifty-eight lipid metabolism-related differentially expressed genes between high-risk NB and non-high-risk NB in the GSE49710 dataset were analyzed using bioinformatics, including 45 down-regulated genes and 13 up-regulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified steroid hormone biosynthesis as an abnormal metabolic pathway in high-risk NB. Survival analysis established a three-gene prognostic model, including ACHE, GDPD5 and PIK3R1. In the test data, the AUCs of the established prognostic models used to predict patient survival at 1, 3 and 5 years were 0.84, 0.90 and 0.91, respectively. Finally, in the SH-SY5Y cell line, it was verified that overexpression of GDPD5 can inhibit cell proliferation and migration, as well as affect the lipid metabolism of SH-SY5Y, but not the sugar metabolism. hsa-miR-592 was predicted to be a potential target miRNA of GDPD5 by bioinformatics. In conclusion, this study develops a lipid-metabolism-related gene-based prognostic model for NB and demonstrates that GDPD5 inhibits SH-SY5Y proliferation and migration and may be targeted by hsa-miR-592 and inhibit SH-SY5Y fat synthesis.

Glycyrrhetinic acid prevents acetaminophen-induced acute liver injury via the inhibition of CYP2E1 expression and HMGB1-TLR4 signal activation in mice.

Acetaminophen (APAP) is a widely used antipyretic and analgesic drug, which is safe and effective at the therapeutic dose. Unfortunately, excessive dosage of APAP could cause severe liver injury due to lack of effective therapy. Successful therapeutic strategies are urgently requested in clinic. Glycyrrhetinic acid (GA), derived from a traditional medicine licorice, has been shown to exert anti-inflammatory and antioxidant actions. In this study, the effect and the underlying mechanism of GA on APAP-induced hepatotoxicity were explored. Our results showed that pretreatment with GA significantly reduced serum ALT and AST activities, alleviated hepatic pathological damages with hepatocellular apoptosis, down-regulated expression of CYP2E1 mRNA and protein, increased GSH levels, and reduced reactive oxygen species (ROS) productions in the liver of APAP-exposed mice. Furthermore, GA obviously inhibited APAP-induced HMGB1-TLR4 signal activation, as evaluated by reduced hepatic HMGB1 release, p-IRAK1, p-MAPK and p-IκB expression as well as the productions of TNF-α and IL-1ß. In addition, GA attenuated hepatic neutrophils recruitment and macrophages infiltration caused by APAP. These findings reflected that GA could alleviate APAP-induced hepatotoxicity, the possible mechanism is associated with down-regulation of CYP2E1 expression and deactivation of HMGB1-TLR4 signal pathway.

MSX2 Induces Trophoblast Invasion in Human Placenta.

Normal implantation depends on appropriate trophoblast growth and invasion. Inadequate trophoblast invasion results in pregnancy-related disorders, such as early miscarriage and pre-eclampsia, which are dangerous to both the mother and fetus. Msh Homeobox 2 (MSX2), a member of the MSX family of homeobox proteins, plays a significant role in the proliferation and differentiation of various cells and tissues, including ectodermal organs, teeth, and chondrocytes. Recently, MSX2 was found to play important roles in the invasion of cancer cells into adjacent tissues via the epithelial-mesenchymal transition (EMT). However, the role of MSX2 in trophoblastic invasion during placental development has yet to be explored. In the present study, we detected MSX2 expression in cytotrophoblast, syncytiotrophoblast, and extravillous cytotrophoblast cells of first or third trimester human placentas via immunohistochemistry analysis. Furthermore, we found that the in vitro invasive ability of HTR8/SVneo cells was enhanced by exogenous overexpression of MSX2, and that this effect was accompanied by increased protein expression of matrix metalloproteinase-2 (MMP-2), vimentin, and ß-catenin. Conversely, treatment of HTR8/SVneo cells with MSX2-specific siRNAs resulted in decreased protein expression of MMP-2, vimentin, and ß-catenin, and reduced invasion levels in a Matrigel invasion test. Notably, however, treatment with the MSX2 overexpression plasmid and the MSX2 siRNAs had no effect on the mRNA expression levels of ß-catenin. Meanwhile, overexpression of MSX2 and treatment with the MSX2-specific siRNA resulted in decreased and increased E-cadherin expression, respectively, in JEG-3 cells. Lastly, the protein expression levels of MSX2 were significantly lower in human pre-eclamptic placental villi than in the matched control placentas. Collectively, our results suggest that MSX2 may induce human trophoblast cell invasion, and dysregulation of MSX2 expression may be associated with pre-eclampsia.

Inhibition of Liver Carcinoma Cell Invasion and Metastasis by Knockdown of Cullin7 In Vitro and In Vivo.

Cullin7 is an E3 ubiquitin ligase. The Cullin7 protein family functions as a molecular scaffold to coordinate substrate ubiquitination in Skp, Cullin, and F-box-containing complex (SCF complex). Cullin7s control normal development and primary cellular processes and are characterized by a unique genomic network organization. Less is known about the involvement of Cullin7 with hepatocellular carcinoma (HCC). In this study, we found that Cullin7 showed a high expression in HCC tumor tissues, especially in metastatic HCC tumor tissues. Also, there was a negative correlation between Cullin7 expression and long survival. Silencing of Cullin7 in liver cancer cells can significantly reduce the migration, invasion, and metastatic abilities. Also, detection of epithelial-mesenchymal transition (EMT) marker expression showed that Cullin7 promotes epithelial-mesenchymal transformation of cancer cells. The results of this study helped to elucidate the oncogene functions of Cullin7 in liver cancers.

Aberrant expression of clock gene period1 and its correlations with the growth, proliferation and metastasis of buccal squamous cell carcinoma.

Period1 (PER1) is an important core clock gene, which regulates normal cell proliferations and physiological rhythms of human beings. Recent studies have showed aberrant expressions and altered rhythms of PER1 were highly correlated to the carcinogenesis and development of malignant tumors. However, there is no study on the correlation of aberrant expressions and altered rhythms of PER1 with the growth, proliferation and metastasis of buccal squamous cell carcinoma (BSCC). In this study, PER1 and MMP-2 expression in the cancerous and adjacent noncancerous tissues of 38 patients with BSCC and its correlations with patients' clinical pathologic characteristics were investigated. A mouse model of BSCC was also established and mice were sacrificed at 4 different time points in a period of 24 hours. Xenografted tumor weight, proliferation index (PI), and mitotic index (MI) of tumors in the 4 time groups were detected. Results showed that PER1 expression was significantly down-regulated in cancerous tissues of patients with BSCC (P<0.05). PER1 expression was significantly down-regulated in patients of T3∼T4 staging and those with lymph node metastasis compared to that of T1∼T2 staging and those without lymph node metastasis (P<0.05), respectively. PER1 mRNA expression, MI and tumor weight had significant differences among the 4 time groups, which PI all confirmed to circadian rhythms. MI, PI, MMP-2 mRNA and tumor weight had negative correlation with PER1 mRNA expression. Peak value of PER1 mRNA expression and trough values of MI, PI and tumor weight all appeared in middle activity phase, whereas trough value of PER1 mRNA expression and peak values of MI, PI and tumor weight all occurred in middle rest phase. Our study suggested that aberrant expression of PER1 had significant correlation with the growth, proliferation and metastasis of BSCC and it might act as an anti-oncogene.