HOXB13 promotes proliferation,migration, and invasion of glioblastoma through transcriptional upregulation of lncRNA HOXC-AS3

HOXB13 exerts a close relation in several human cancers. This study explored the role of HOXB13 in glioblastoma (GBM), a brain tissue with the highest aggressive rate and mortality in adults. Through microarray and immunohistochemistry analyses, HOXB13 was highly expressed in GBM tissues. Furthermore, we showed that high-level expression of HOXB13 in GBM was associated with worse survival, suggesting that HOXB13 could be a prognostic marker for patients with GBM. GBM cells U87 and U251 overexpressing HOXB13 showed enhanced proliferation, migration, and invasion relative to the control cells, while knockdown of HOXB13 led to decreased cell proliferation, migration, and invasion abilities. In addition, dual-luciferase report assay, chromatin immunoprecipitation assay, and quantitative real-time polymerase chain reaction data showed that HOXB13 directly bound to HOXC-AS3 promoter. HOXC-AS3 was involved in HOXB13-induced proliferation, migration, and invasion of GBM cells. In summary, this study revealed the prognostic potential of HOXB13 in GBM. We believed that HOXB13/HOXC-AS3 signaling axis can be served as therapeutic targets for this highly aggressive cancer.     

Gene expression profile of the hippocampus of rats subjected to traumatic brain injury

Traumatic brain injury (TBI) is a serious public health problem as well as a leading cause of severe posttraumatic disability. Numerous studies indicate that the differentially expressed genes (DEGs) of neural signaling pathways are strongly correlated with brain injury. To further analyze the roles of the DGEs in the central nervous system, here we systematically investigated TBI on the hippocampus and its injury mechanism at the whole genome level. On the basis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Analyses, we revealed that the DEGs were involved in many signaling pathways related to the nervous system, especially neuronal survival-related pathways. Finally, we verified the microarray results and detected the gene expression of neuronal survival-related genes in the hippocampus by using real-time quantitative polymerase chain reaction. With Western blot and axon growth assay, the expression of P2rx3 was upregulated in rats subjected to TBI, and overexpression of P2rx3 promoted neurite growth of NG108 cells. Our results suggested that the DEGs (especially P2rx3) and several signaling pathways might play a pivotal role in TBI. We also provided several targeted genes related to TBI for future investigation.     

Shared KEGG pathways of icariin-targeted genes and osteoarthritis

The beneficial effects of icariin in the management of many diseases, such as chronic renal failure and heart failure, are well known. Icariin has also been shown to ameliorate osteoarthritis (OA) symptoms; however, the underlying mechanisms remain unclear. In this study, a bioinformatics analysis was performed to investigate the KEGG pathways of icariin-targeted genes involved in OA. Our study suggests that icariin plays a role in OA by regulating inflammatory cytokine production, insulin resistance, and cell survival through modulation of the NF-κB, MAPK, and Akt signaling pathways. Importantly, IKBKB, NFKBIA, MAPK8, MAPK9, and MAPK10 may be the hub genes affected by icariin when providing its beneficial effects on OA. In addition, we found that icariin decreases proinflammatory factors and inhibits chondrocyte apoptosis through suppression of the NF-κB pathway. Our study highlights a set of KEGG pathways that could explain the molecular mechanism of icariin's action on OA, suggesting that icariin could be considered as a promising therapeutic option for OA.     

Microvesicles-mediated communication between endothelial cells modulates,endothelial survival,and angiogenic function via transferring of miR-125a-5p

Endothelial cells (ECs) released microvesicles (EMVs) could modulate the functions of target cells by transferring their microRNAs (miRs). We have reported that miR-125a-5p protected EC function. In this study, we determined whether EMVs provided beneficial effects on ECs by transferring miR-125a-5p. Human brain microvessel ECs were transfected with miR-125a-5p mimic or miR-125a-5p short hairpin RNA to obtain miR-125a-5p overexpressing ECs and miR-125a-5p knockdown ECs, and their derived EMVs. For the functional study, ECs or hypoxia/reoxygenation injured ECs were coincubated with various EMVs. The survival and angiogenic function of ECs were measured. Western blot and quantitative real time polymerase chain reaction (qRT-PCR) were used for measuring the levels of phosphoinositide 3-kinase (PI3K), phosphorylation-Akt (p-Akt)/Akt, p-endothelial nitric oxide synthase (p-eNOS), cleaved caspase-3, and miR-125a-5p. PI3K inhibitor was used for pathway analysis. EMVs promoted the proliferation, migration, and tube formation ability of ECs, and alleviated the apoptotic rate of ECs. These effects were associated by an increase in p-Akt/Akt and p-eNOS, and a decrease in cleaved caspase-3 could be abolished by LY294002. Overexpression or downregulation of miR-125a-5p in EMVs promoted or inhibited those effects of EMVs. EMVs could enhance the survival and angiogenic function of ECs via delivering miR-125a-5p to modulate the expression of PI3K/Akt/eNOS pathway and caspase-3.