SET7/9 promotes H3K4me3 at lncRNA DRAIC promoter to modulate growth and metastasis of glioma.

OBJECTIVE: We aimed at investigating the expression levels of SET7/9 in glioma and the relationship between SET7/9 and LncRNA DRAIC. Further, we explored the relationship between SET7/9 and glioma cell metastasis and mood. PATIENTS AND METHODS: The expression levels of DRAIC and miR-18a-3p in gastric cancer cells were measured by quantitative polymerase chain reaction (qPCR). The binding site of the promoter of DRAIC by H3K4me3 was confirmed by ChIP-Real-time PCR. The direct target of DRAIC and miR-18a-3p in gastric cancer cells was measured by a Luciferase reporter assay. Cell proliferation was detected by Cell counting kit-8 (CCK8), and cell invasion and migration were measured by transwell assays. RESULTS: Compared with adjacent non-cancerous normal tissues, SET7/9 and DRAIC were both downregulated and miR-18a-3p was upregulated in glioma cells. Meanwhile, silencing of SET7/9 enhanced cell proliferation, migration, and invasion in U251 cells. H3K4me3 protein can bind to DRAIC promoter directly. Inhibition of SET7/9 and downregulation of DRAIC in U251 cells reversed the effect of SET7/9 silencing on the growth and metastasis of glioma cells. In U251 cells, SET7/9 and DRAIC overexpression inhibited cell proliferation, migration and invasion. In addition, miR-18a-3p interacts with DRAIC through direct binding. The inhibition of DRAIC promoted the growth and metastasis of U251 cells, while the co-transfection of si- DRAIC and miR-18a-3p further promoted the growth and metastasis of U251 cells. Overexpression of DRAIC inhibited the growth and metastasis of cells, completely reversing the co-transfection of Lnc-DRAIC and miR-18a-3p. CONCLUSIONS: In this research, we discovered that the expression of SET7/9 was low in glioma cells and SET7/9-mediated H3K4me3 enrichment on the DRAIC promoter regulated the growth and metastasis of glioma cells by targeting miR-18a-3p. It potentially provides a new therapeutic marker targeting glioma.

Expressions and significance of calcitonin gene-related peptide and nerve growth factor in rabbit model of traumatic brain injury complicated with tibial fracture: preliminary results.

OBJECTIVE: This paper aims to establish the rabbit model of traumatic brain injury (TBI) complicated with tibial fracture and to investigate the expressions and significance of calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF) in cerebrospinal fluid (CSF) and serum. MATERIALS AND METHODS: 60 rabbits were randomly divided into control group, TBI group, fracture group (F group), and TBI complicated with fracture group (TBI+F group), with 15 white rabbits in each group. After modeling, the expression levels of CGRP and NGF in the CSF, and serum were detected. At the 7th week after the operation, X-ray was used to evaluate the healing of fracture rabbits. RESULTS: Serum NGF content was compared among groups at the same time point. TBI+F group had significantly higher serum NGF content than the other three groups at each time point after the operation (p<0.05). From the 3rd day after the operation, TBI group and F group had significantly higher serum NGF content than control group (p<0.05). On the 7th and 14th days after the operation, TBI group had significantly higher serum NGF content than the F group (p<0.05). The CSF NGF content in TBI group and TBI+F group showed an upward trend, and it was higher in TBI+F group and TBI group than that in F group and control group from the 7th day (p<0.05). On the 0th and 3rd days, TBI+F group had significantly higher serum NGF content than the other three groups (p<0.05). TBI+F group had a significantly higher healing number than F group on the 14th day (p<0.05). CONCLUSIONS: NGF and CGRP are mainly present in the CSF. When TBI complicated with F occurs, the serum NGF and CGRP increase, which may be involved in the fracture healing.

Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-ß1).

OBJECTIVES: The role of mechanical stress and transforming growth factor beta 1 (TGF-ß1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known. METHODS: In this study, TGF-ß1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-ß1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours. RESULTS: A significant decrease in the survival rate of co-cultured chondrocytes was found. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay demonstrated that mechanical stress-induced apoptosis occurred significantly in co-cultured chondrocytes but administration of the TGF-ß1 receptor inhibitor, SB-505124, can significantly reverse these effects. Abdominal administration of SB-505124 can attenuate markedly articular cartilage degradation in OA rats. CONCLUSION: Mechanical stress-induced overexpression of TGF-ß1 from osteoclasts is responsible for chondrocyte apoptosis and cartilage degeneration in OA. Administration of a TGF-ß1 inhibitor can inhibit articular cartilage degradation.Cite this article: R-K. Zhang, G-W. Li, C. Zeng, C-X. Lin, L-S. Huang, G-X. Huang, C. Zhao, S-Y. Feng, H. Fang. Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-ß1). Bone Joint Res 2018;7:587-594. DOI: 10.1302/2046-3758.711.BJR-2018-0057.R1.

Differential expression profiling of microRNAs in para-carcinoma, carcinoma and relapse human pancreatic cancer

Purpose: To explore the altered different expression of miRNAs and the mechanisms underlying the relapse and metastasis of pancreatic cancer. Materials and methods: The most differentially expressed miRNAs were analyzed by gene ontology (GO) term analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and protein interaction analysis. The potentially regulated target genes of the most differentially expressed miRNAs were also analyzed further by GO term analysis and KEGG pathway analysis, and quantitated by qRT-PCR. Results: In total, we found 12 miRNAs displayed at least a 30-fold increase or decrease in expression of carcinoma and relapse vs. para-carcinoma human pancreatic cancer (C/R vs. P). In addition, our study found that pancreatic cancer was related to pathways in cancer, including Jak-STAT signaling pathway, MAPKsignaling pathway and PPAR signaling pathway. Conclusions: The differential expressed miRNAs and their predicted target genes that involved in Jak-STAT signaling pathway, MAPK signaling pathway and PPAR signaling pathway indicating their potential roles in pancreatic carcinogenesis and progress (AU)

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Differential expression profiling of microRNAs in para-carcinoma, carcinoma and relapse human pancreatic cancer.

PURPOSE: To explore the altered different expression of miRNAs and the mechanisms underlying the relapse and metastasis of pancreatic cancer. MATERIALS AND METHODS: The most differentially expressed miRNAs were analyzed by gene ontology (GO) term analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and protein interaction analysis. The potentially regulated target genes of the most differentially expressed miRNAs were also analyzed further by GO term analysis and KEGG pathway analysis, and quantitated by qRT-PCR. RESULTS: In total, we found 12 miRNAs displayed at least a 30-fold increase or decrease in expression of carcinoma and relapse vs. para-carcinoma human pancreatic cancer (C/R vs. P). In addition, our study found that pancreatic cancer was related to pathways in cancer, including Jak-STAT signaling pathway, MAPK signaling pathway and PPAR signaling pathway. CONCLUSIONS: The differential expressed miRNAs and their predicted target genes that involved in Jak-STAT signaling pathway, MAPK signaling pathway and PPAR signaling pathway indicating their potential roles in pancreatic carcinogenesis and progress.