No abstract

Through their multiple targets, microRNAs (miRNAs) are involved in numerous physiological and pathological processes. In this study, miR‐342‐3p was found to be deregulated with ossification of ligament or osteoporosis. We demonstrate that silencing miR‐342‐3p impairs osteoblast activity and matrix mineralization, while over expression of miR‐342‐3p promotes osteoblast differentiation significantly. Moreover, miR‐342‐3p directly targets activating transcription factor 3 (ATF3), which inhibits transcription of pro‐osteogenic differentiation‐associated genes. In addition, there exists a higher frequency of methylation at the CpG island of the Enah/Vasp‐Like (EVL) locus in undifferentiated pre‐osteoblasts; however, demethylation of the EVL CpG island induces over expression of miR‐342‐3p during osteogenic differentiation. This study suggests that miR‐342‐3p may serves as a potential marker for diagnosis and treatment of ossification of ligament and osteoporosis.

Ossification of the ligamentum flavum (OLF) is a common spinal disorder that causes myelopathy and radiculopathy. Non-coding RNAs (ncRNAs) are involved in numerous pathological processes; however, very few ncRNAs have been identified to be correlated with OLF. Here we compared the expression of lncRNA, mRNA, circRNA, and microRNA in OLF tissues from OLF patients and healthy volunteers through mRNA, lncRNA, and circRNA microarrays and microRNA sequencing. A total of 2,054 mRNAs, 2,567 lncRNAs, 627 circRNAs, and 28 microRNAs (miRNAs) were altered during the process of OLF. qPCR confirmed the differential expression of selected mRNAs and ncRNAs. An lncRNA-mRNA co-expression network, miRNA-mRNA target prediction network, and competing endogenous RNA (ceRNA) network of circRNA-miRNA-mRNA were constructed based on a correlation analysis of the differentially expressed RNA transcripts. Subsequently, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for the differentially expressed mRNAs and the predicted miRNAs target genes were performed. In addition, a deregulated miRNA-19b-3p-based miRNA-circRNA-lncRNA-mRNA network was confirmed, by gain-of-function and loss-of-function experiments, to function in the process of ossification. Taken together, this study provides a systematic perspective on the potential function of ncRNAs in the pathogenesis of OLF.

No abstract

N-myc downstream regulated gene 1 (NDRG1) has been well characterized as a suppressor of metastasis in numerous types of carcinoma. NDRG1 inhibits the metastatic progression of cancer cells via its inhibitory effects on a wide variety of cellular signaling pathways. Vasculogenic mimicry (VM) refers to the unique ability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks, and is the main reason for the poor prognosis and failure of antivascular therapy in gastric carcinoma (GC). Tumor cells can mimic the function of endothelial cells to exhibit VM through epithelial-mesenchymal transition (EMT). However, the potential function of NDRG1 in metastatic GC progression in patients has not yet been fully elucidated. To date, data regarding the function of NDRG1 in VM formation in GC have not been reported. The aim of the present study was to elucidate these unknown areas. To this end, 228 samples of human GC were used to identify the protein expression levels of NDRG1, VM-associated proteins and EMT-associated proteins via immunohistochemistry, and their clinical significance was assessed. In addition, the data of 415 patients with GC were collected from The Cancer Genome Atlas database. A functional enrichment analysis concerning NDRG1 was performed using Metascape and the Gene Set Enrichment Analysis (GSEA). In conclusion, the results of the present study indicate that NDRG1 is negatively correlated with poor prognosis through suppression of VM formation in GC. The results of the present study demonstrated that NDRG1 decreases EMT-associated protein expression and that HER2 expression may serve a significant role in this process. The Metascape and GSEA results also indirectly support this conclusion. The present study discusses the status NDRG1 as a prognostic and selective biomarker in GC, as well as current and future NDRG1-targeted therapies.