Recent studies have closely associated exosomal microRNAs (miRNAs) with various human diseases, including diabetes mellitus (DM), which is a complex multifactorial metabolic disorder disease. In the diabetic condition, exosomal miR-NAs are taken up by recipient cells, where they exert their biological function and thereby modulate the progression of DM-associated complications, including diabetic retinopathy (DR), diabetic macrovascular complications (DMCs), diabetic nephropathy (DN), diabetic foot ulcer (DFU), diabetic peripheral neuropathy (DPN), and diabetic cardiomyopathy (DCM).
Recent studies have reported that long non-coding RNAs (lncRNAs) are associated with the tumourigenesis of colorectal cancer (CRC); however, several of these are yet to be identified and characterised. In this study, we report a novel lncRNA, LINC00467, which was significantly up-regulated in CRC; we investigated its function and mechanism in CRC. Our study demonstrated that LINC00467 levels in 45 pairs of CRC tissues were higher than those in the corresponding normal colon mucosal tissues. We used the Gene Expression Omnibus (GEO) and Gene Expression Profiling Interactive Analysis (GEPIA) databases for the analysis and measurement of clinical samples, and observed that the CRC patients with high LINC00467 expression levels showed poor overall survival (OS) and recurrent-free survival (RFS) rates. Furthermore, following the short interfering RNA (siRNA) knockdown of LINC00467 in the CRC cell line, the results demonstrated that LINC00467 suppresses the proliferation, invasion and metastasis of CRC cells in vitro. Moreover, its molecular mechanism of LINC00467 decreased the expression of Cyclin D1, Cyclin A1, CDK2, CDK4 and Twist1 as well as enhanced the expression of E-cadherin. Collectively, these findings suggest that LINC00467 may be crucial in the progression and development of CRC, and may serve as a potential therapeutic target for CRC patients.
Emerging evidence indicates that long noncoding RNAs (lncRNAs) are closely associated with colorectal cancer (CRC) tumorigenesis. One example is lncRNA Deleted in Lymphocytic Leukemia 2 ( DLEU2 ). However, how DLEU2 contributes to CRC is still poorly understood. This study sought to investigate the effects of DLEU2 on CRC pathogenesis, and the underlying mechanism involved. Using a quantitative real-time polymerase chain reaction (qRT-PCR) assay, we demonstrated that the expression levels of DLEU2 in 45 pairs of CRC tissues were higher than those in the corresponding normal colon mucosal tissues. In addition, CRC patients with high DLEU2 expression levels exhibited poor overall survival (OS) and recurrence-free survival (RFS), as determined by analyses and measurements from the GEO and GEPIA databases. When DLEU2 was silenced using short interfering RNA (siRNA) in CRC cell line, the results demonstrated that DLEU2 silencing suppressed CRC cell tumorigenesis in vitro, which was associated with decreased expression of cyclin dependent kinase 6(CDK6), ZEB1, and ZEB2 as well as enhancing the expression of Cyclin-dependent kinase inhibitor 1A (CDKN1A). Taken together, the results of this study suggested that DLEU2 may play critical roles in the progression of CRC and may serve as a prognostic biomarker for CRC.
Circular RNAs(CircRNAs), a new class of non‐coding RNAs, possess significant capabilities of gene regulation and are disrupted in various diseases, including diabetes mellitus (DM). However, the underlying mechanism of CircRNAs in DM and diabetic complications remains illusive. A recent study published by Liu et al. (Proc Natl Acad Sci USA 116:7455–7464, 2019) shown that a novel diabetic retinopathy (DR)‐associated CircRNA cPWWP2A, which could act as a competing endogenous RNA interacting with miR‐579 to promote the DR‐induced retinal vascular dysfunction through up‐regulating the expression of Angiopoietin 1, Occludin, and SIRT1. Their findings may provide new insight into the potential use of CircRNA cPWWP2A for the targeted therapy of DR. However, those promising findings may need to be further evaluated detailedly for the following reason. (1) This study doesn’t well clarify why the most significantly up‐regulated CircRNA mmu _circ_0000254 the fold change of which is 160.581 is excluded,while the cPWWP2A the fold change of which is only 3.487 is chosen. (2) It is difficult to conclude that cPWWP2A competing with miR‐579 only by the analysis of colocalization in pericytes.
As life expectancy increases, Osteoarthritis (OA) is becoming a more frequently seen chronic joint disease. The main characteristics of OA are loss of articular cartilage, subchondral bone sclerosis, and synovial inflammation. Baicalein (Bai), a traditional Chinese medicine extracted from Scutellaria baicalensis Georgi, has been demonstrated to exert notable anti-inflammatory effects in previous studies, suggesting its potential effect in the treatment of OA. In this study, we first predicted the action targets of Bai, mapped target genes related to OA, identified potential anti-OA targets for Bai, performed gene ontology (GO) enrichment, and KEGG signaling pathway analyses of the action targets, and analyzed the molecular docking of key Bai targets. Additionally, the effect and potential mechanism of Bai against OA were verified in mouse knee OA models induced by destabilized medial meniscus (DMM) surgery. GO and KEGG analyses showed that 19 anti-OA targets were mainly involved in the response to oxidative stress, the response to hypoxia and apoptosis, and the PI3K-Akt and p53 signaling pathways. Molecular docking results indicated that BAX, BCL 2, and Caspase 3 enriched in the apoptotic signaling pathway have high binding affinity with Bai. Validation experiments showed that Bai can significantly attenuate the loss of articular cartilage (OARSI score), suppress synovial inflammation (synovitis score), and ameliorate subchondral bone resorption measured by micro-CT. In addition, Bai notably inhibited the expression of apoptosis-related proteins in articular cartilage (BAX, BCL 2, and Caspase 3). By combining network pharmacology with experimental validation, our study identifies and verifies the importance of the apoptotic signaling pathway in the treatment of OA by Bai. Bai may have promising application and potential therapeutic value in OA treatment.
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