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Several circular RNAs (circRNAs) may have role important roles in biological processes, however, there is limited knowledge of circRNAs and their potential functions in RAW264.7 macrophages. The present study aimed to examine the expression of circRNAs and explore their effects on interleukin-6 (IL-6) expression induced by calcitonin gene-related peptide (CGRP) in RAW264.7 macrophages. To identify circRNAs, the circRNA expression was measured in macrophages with or without CGRP stimulation. The interaction between circRNAs and microRNAs (miRs) were then identified using bioinformatic software and networks. In the current study, it was demonstrated that CGRP increased the expression of IL-6 mRNA in a dose- and time-dependent manner. Furthermore, mmu_circRNA_007893 was significantly increased in the CGRP-stimulated macrophages. Silencing of mmu_circRNA_007893, IL-6 mRNA expression was significantly decreased, whereas mmu-miR-485-5p expression was markedly increased. Furthermore, when overexpression of mmu-miR-485-5p, IL-6 mRNA was markedly decreased. The results demonstrated that CGRP-induced IL-6 mRNA expression was mediated by mmu_circRNA_007893, and mmu_circRNA_007893 functioned as an endogenous mmu-miR-485-5p sponge as part of induction of IL-6 mRNA expression. [ABSTRACT FROM AUTHOR]

Bio-Ossα and α-calcitonin gene-related peptide (CGRP) are involved in osteogenesis. However, it has remained to be assessed how α-CGRP affects the effect of Bio-Oss. In the present study, primary osteoblasts were incubated with α-CGRP, Bio-Oss, α-GGRP-Bio-Oss or mimic-α-CGRP. The proliferation rate, mineralization nodules, alkaline phosphatase (ALP) activity and the expression of osteogenic genes were measured by a Cell Counting Kit-8 assay, Alizarin Red-S staining, ALP activity detection and reverse-transcription quantitative PCR as well as western blot analysis, respectively. The proliferation rate, ALP activity and the number of mineralization nodules were significantly increased in the α-CGRP-modified Bio-Oss group compared to that in the Bio-Oss group. The mRNA and protein levels of osteocalcin, Runt-related transcription factor-2 and ALP were significantly upregulated in the α-CGRP-Bio-Oss group compared with those in the Bio-Oss group. Furthermore, the effect of mimic-α-CGRP on osteogenesis was reduced as it carried a mutation. In conclusion, the present study was the first to demonstrate that Bio-Oss modified with CGRP contributed to osteogenesis and may provide a novel formulation applied in the clinic for restoration of large bone defects. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a class of non-coding RNAs that exhibit important regulatory roles in various biological processes. However, the role of circRNAs and their potential role in osteoblast differentiation and mineralization is unclear. The aim of the present study was to investigate the expression of mmu_circ_003795 and its effect on collagen type XV α 1 chain (COL15A1). First, it was identified that the expression levels of mmu_circ_003795 and osteopontin (OPN) were upregulated in the induced cells. Silencing of mmu_circ_003795 reduced the gene and protein levels of COL15A1 and OPN, whereas the expression level of mmu-microRNA (miR)-1249-5p was upregulated. In addition, after 7 or 14 days of induction, alkaline phosphatase and Alizarin Red-S staining were decreased in the mmu_circRNA_003795 inhibitory group compared with the negative control group. In conclusion, mmu_circ_003795 may regulate osteoblast differentiation and mineralization in MC3T3-E1 and MDPC23 cells via mmu-miR-1249-5p by targeting COL15A1. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that the epigenetic alterations caused by histone modifications have important roles in the genesis of gastric cancer (GC), particularly the well-studied acetylation and methylation modifications. In the present study, a Bioinformatics analysis of the expression of histone modification-associated genes in GC and normal tissues was performed by using datasets from Oncomine, the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). The clinical data of GC patients were downloaded from TCGA to determine the association between histone modification-associated gene expression and clinicopathological parameters or survival of GC. Finally, lysine acetyltransferase 2A (KAT2A), nuclear receptor coactivator 1 (NCOA1), SMYD family member 5 (SMYD5), protein arginine methyltransferase 1 (PRMT1) and PRDF1-RIZ (PR)/Su(var)3-9, enhancer-of-zeste and trithorax (SET) domain 16 (PRDM16) were screened; KAT2A, SMYD5 and PRMT1 were upregulated, while PRDM16 expression was downregulated in GC. Analysis of the GEO and Oncomine datasets revealed that NCOA1 was upregulated, which was contrary to the result obtained with the TCGA stomach adenocarcinoma dataset. Aberrant expression of KAT2A, NCOA1, SMYD5 and PRMT1 was more obvious in gastric intestinal-type adenocarcinoma; low NCOA1 expression was associated with better overall survival of GC patients [hazard ratio (HR)=0.690, 95% CI=0.570–0.840, P<0.001] and was an independent predictor for patients diagnosed with GC (HR=0.639, 95% CI=0.437–0.933, P=0.020). Correlation analysis and protein-protein interaction network analysis indicated a close association between ATAD2 and estrogen receptor 1 (ESR1), PRMT1, NCOA1 and KAT2A. In conclusion, differential expression of KAT2A, NCOA1, SMYD5, PRMT1 and PRDM16 was identified in GC vs. normal tissues, low NCOA1 expression was associated with poor survival of GC and ATAD2 may interact with ESR1 to regulate NCOA1 and PRMT1 in GC. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a class of non-coding RNAs that may have important regulatory potency in various biological processes. However, the role of circRNAs and their potential functions in bone marrow mesenchymal stem cells of mice (BMSCs) are still ambiguous. The current study aims to examine the expression of circRNAs and to investigate their effects on FOS like 2 AP-1 transcription factor subunit (FOSL2) expression following stimulation of BMSCs with calcitonin gene-related peptide (CGRP). RNA generated from BMSCs stimulated with or without CGRP was used in a microarray to detect expression of circRNAs. There were 58 significantly differentially expressed circRNAs following CGRP treatment, with 44 circRNAs downregulated and 14 upregulated. Bioinformatics analysis and regulatory networks were used to identify the potential interactions between circRNAs and microRNAs (miRs). mmu_circRNA_003795 was significantly increased in the CGRP-stimulated BMSCs compared with the blank control. Silencing of mmu_circRNA_003795, significantly increased the expression of mmu_miR-504-3p, whereas FOSL2 expression and cell proliferation were decreased. Furthermore, silencing of mmu_mir-504-3p using an miR inhibitor led to increased FOSL2 expression. Additionally, silencing of mmu_circRNA_003795 using small interfering RNA induced marked alterations in the cell cycle of BMSCs. The results demonstrated that mmu_circRNA_003795 can indirectly regulate FOSL2 expression via sponging of miR-504-3p, resulting in alterations in BMSC proliferation. [ABSTRACT FROM AUTHOR]