Pancreatic cancer (PC) is a malignant tumor that is difficult to diagnose and treat. Circular RNAs (circRNAs) are biomarkers that may be used to diagnose certain cancers or act as targets for cancer treatment. We aimed to explore the functions of human circular RNA 001587 (hsa_circRNA_001587) on the progression of PC and the underlying mechanism. The expression pattern of hsa_circRNA_001587 and microRNA-223 (miR-223) in PC tissues and cells was determined by RT-qPCR. Dual-luciferase reporter gene assay, RNA-pull down, Argonaute 2 (AGO2) immunoprecipitation assay, and Northern blot analysis were applied to verify the binding relationships among hsa_circRNA_001587, miR-223 and solute carrier family 4 member 4 (SLC4A4). Further analysis of their roles was performed in PC cell line PANC-1. Moreover, we either downregulated or upregulated the expression of hsa_circRNA_001587, miR-223 and SLC4A4 by transfection in vitro. A mouse xenograft model of PC cells was established to evaluate tumor growth in vivo. Hsa_circRNA_001587 was poorly expressed but miR-223 was highly expressed in PC tissues and cell lines. Up-regulation of hsa_circRNA_001587 downregulated the expression of MMP-2, MMP-9, MCM2 and VEGF, and decreased the proliferation, migration, invasion, angiogenic and tumorigenic abilities of PC cells. MiR-223, which can bind with hsa_circRNA_001587, reversed the effects of hsa_circRNA_001587 on PC cells. In addition, SLC4A4 was identified as a target of miR-223, and its knockdown could counteract the regulatory effects of overexpressed hsa_circRNA_001587 or inhibited miR-223 expression on PC cells. Therefore, hsa_circRNA_001587 inhibits PC cell migration, invasion, angiogenesis and tumorigenesis by impairing miR-223-mediated SLC4A4 inhibition.
This study investigated the role of microRNA-95 (miR-95) in gastric cancer (GC) and to elucidate the underlying mechanism. Initially, bioinformatic prediction was used to predict the differentially expressed genes and related miRNAs in GC. miR-95 and DUSP5 expression was altered in GC cell line (MGC803) to evaluate their respective effects on the epithelial-mesenchymal transition (EMT) process, cellular processes (cell proliferation, migration, invasion, cell cycle, and apoptosis), cancer stem cell (CSC) phenotype, as well as tumor growth ability. It was further predicted in bioinformatic prediction and verified in GC tissue and cell line experiments that miR-95 was highly expressed in GC. miR-95 negatively regulated DUSP5, which resulted in the MAPK pathway activation. Inhibited miR-95 or overexpressed DUSP5 was observed to inhibit the levels of CSC markers (CD133, CD44, ALDH1, and Lgr5), highlighting the inhibitory role in the CSC phenotype. More important, evidence was obtained demonstrating that miR-95 knockdown or DUSP5 upregulation exerted an inhibitory effect on the EMT process, cellular processes, and tumor growth. Together these results, miR-95 knockdown inhibited GC development via DUSP5-dependent MAPK pathway. K E Y W O R D S cancer stem cell phenotype, DUSP5, epithelial-mesenchymal transition, gastric cancer, MAPK pathway, microRNA-95
Myasthenia gravis (MG) is an autoantibody-mediated disease of the neuromuscular junction (NMJ). However, accumulating evidence has indicated that MG patients whose serum anti-acetylcholine receptor (AChR) antibodies are not detectable (serumnegative MG; SNMG) in routine assays share similar clinical features with anti-AChR antibody-positive MG patients. We hypothesized that SNMG patients would have low-affinity antibodies to AChRs that would not be detectable using traditional methods but that might be detected by binding to AChR on the cell membrane, particularly if they were clustered at the high density observed at the NMJ. We expressed AChR subunits with the clustering protein rapsyn (an AChR-associated protein at the synapse) in human embryonic kidney (HEK) cells, and we tested the binding of the antibodies using immunofluorescence. With this approach, AChR antibodies to rapsyn-clustered AChR could be detected in the sera from 45.83% (11/24) of SNMG patients, as confirmed with fluorescence-activated cell sorting (FACS). This was the first application in China of cell-based AChR antibody detection. More importantly, this sensitive (and specific) approach could significantly increase the diagnosis rate of SNMG.
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