Mouse Transforming Growth Factor, Beta 1, Tgfb1 ELISA Kit

Glioblastoma multiforme (GBM) has been considered the most aggressive glioma type. Temozolomide (TMZ) is the main first-line chemotherapeutic agent for GBM. Decreased mutS homolog 6 (MSH6) expression is clinically recognized as one of the principal reasons for GBM resistance to TMZ. However, the specific functions of MSH6 in GBM, in addition to its role in mismatch repair, remain unknown. Methods: Bioinformatics were employed to analyze MSH6 mRNA and protein levels in GBM clinical samples and to predict the potential cancer-promoting functions and mechanisms of MSH6. MSH6 levels were silenced or overexpressed in GBM cells to assess its functional effects in vitro and in vivo. Western blot, qRT-PCR, and immunofluorescence assays were used to explore the relevant molecular mechanisms. Cu-2(OH)PO4@PAA nanoparticles were fabricated through a hydrothermal method. Their MRI and photothermal effects as well as their effect on restraining the MSH6-CXCR4-TGFB1 feedback loop were investigated in vitro and in vivo. Results: We demonstrated that MSH6 is an overexpressed oncogene in human GBM tissues. MSH6, CXCR4 and TGFB1 formed a triangular MSH6-CXCR4-TGFB1 feedback loop that accelerated gliomagenesis, proliferation (G1 phase), migration and invasion (epithelial-to-mesenchymal transition; EMT), stemness, angiogenesis and antiapoptotic effects by regulating the p-STAT3/Slug and p-Smad2/3/ZEB2 signaling pathways in GBM. In addition, the MSH6-CXCR4-TGFB1 feedback loop was a vital marker of GBM, making it a promising therapeutic target. Notably, photothermal therapy (PTT) mediated by Cu-2(OH)PO4@PAA + near infrared (NIR) irradiation showed outstanding therapeutic effects, which might be associated with a repressed MSH6-CXCR4-TGFB1 feedback loop and its downstream factors in GBM. Simultaneously, the prominent MR imaging (T1WI) ability of Cu-2(OH)PO4@PAA could provide visual guidance for PTT. Conclusions: Our findings indicate that the oncogenic MSH6-CXCR4-TGFB1 feedback loop is a novel therapeutic target for GBM and that PTT is associated with the inhibition of the MSH6-CXCR4-TGFB1 loop.

Background: Recently, increasing evidence has uncovered the roles of mRNA-miRNA-lncRNA network in multiple human cancers. However, a systematic mRNA-miRNA-lncRNA network linked to pancreatic cancer prognosis is still absent. Methods: Differentially expressed genes (DEGs) were first identified by mining GSE16515 and GSE15471 datasets. DAVID database was utilized to conduct functional enrichment analysis. Protein-protein interaction (PPI) network was built using STRING database, and hub genes were identified by Cytoscape plug-in CytoHubba. Upstream miRNAs and lncRNAs of mRNAs were predicted by miRTarBase and miRNet, respectively. Expression, survival and correlation analysis for genes, miRNAs and lncRNAs were performed via GEPIA, Kaplan-Meier plotter and starBase. Results: 734 and 180 upregulated and downregulated significant DEGs were identified, respectively. Functional enrichment analysis revealed that they were significantly enriched in focal adhesion, pathways in cancer and metabolic pathways. According to node degree, hub genes in the PPI networks were screened, such as TGFB1 and ALB. Among the top 20 hub genes, 7 upregulated genes and 2 downregulated hub genes had significant prognostic values in pancreatic cancer. 33 miRNAs were predicted to target the 9 key genes. But only high expression of 8 miRNAs indicated favorable prognosis in pancreatic cancer. Then, 90 lncRNAs were predicted to potentially bind to the 8 miRNAs. SCAMP1, HCP5, MAL2 and LINC00511 were finally identified as key lncRNAs. By combination of results from expression, survival and correlation analysis demonstrated that MMP9/ITGB1-miR-29b-3p-HCP5 competing endogenous RNA (ceRNA) sub-network was linked to prognosis of pancreatic cancer. Conclusions: In a word, we established a novel mRNA-miRNA-lncRNA sub-network, among which each RNA may be utilized as a prognostic biomarker of pancreatic cancer.