Increased Expression and Prognostic Significance of BYSL in Melanoma.

We evaluated the BYSL content and underlying mechanism in melanoma (SKCM) overall survival (OS). In this study, we used a comprehensive approach combining bioinformatics tools, including miRNA estimation, quantitative real-time polymerase chain reaction (qRT-PCR) of miRNAs, E3 ligase estimation, STRING analysis, TIMER analysis, examination of associated upstream modulators, protein-protein interaction (PPI) analysis, as well as retrospective and survival analyses, alongside clinical sample validation. These methods were used to investigate the content of BYSL, its methylation status, its relation to patient outcome, and its immunologic significance in tumors. Our findings revealed that BYSL expression is negatively regulated by BYSL methylation. Analysis of 468 cases of SKCM RNA sequencing samples demonstrated that enhanced BYSL expression was associated with higher tumor grade. We identified several miRNAs, namely hsa-miR-146b-3p, hsa-miR-342-3p, hsa-miR-511-5p, hsa-miR-3690, and hsa-miR-193a-5p, which showed a strong association with BYSL levels. Furthermore, we predicted the E3 ubiquitin ligase of BYSL and identified CBL, FBXW7, FZR1, KLHL3, and MARCH1 as potential modulators of BYSL. Through our investigation, we discovered that PNO1, RIOK2, TSR1, WDR3, and NOB1 proteins were strongly associated with BYSL expression. In addition, we found a close association between BYSL levels and certain immune cells, particularly dendritic cells (DCs). Notably, we observed a significant negative correlation between miR-146b-3p and BYSL mRNA expression in SKCM sera samples. Collectively, based on the previously shown evidences, BYSL can serve as a robust bioindicator of SKCM patient prognosis, and it potentially contributes to immune cell invasion in SKCM.

Wang ZZ ，Yao GT ，Wang LZ ，Zhu YJ ，Chen JH ... -  《-》

Integrated analysis to reveal potential therapeutic targets and prognostic biomarkers of skin cutaneous melanoma.

Skin cutaneous melanoma (SKCM) is a malignant tumor with high mortality rate in human, and its occurrence and development are jointly regulated by genes and the environment. However, the specific pathogenesis of SKCM is not completely understood. In recent years, an increasing number of studies have reported the important role of competing endogenous RNA (ceRNA) regulatory networks in various tumors; however, the complexity and specific biological effects of the ceRNA regulatory network of SKCM remain unclear. In the present study, we obtained a ceRNA regulatory network of long non-coding RNAs, microRNAs, and mRNAs related to the phosphatase and tensin homolog (PTEN) in SKCM and identified the potential diagnostic and prognostic markers related to SKCM. We extracted the above three types of RNA involved in SKCM from The Cancer Genome Atlas database. Through bioinformatics analysis, the OIP5-AS1-hsa-miR-186-5p/hsa-miR-616-3p/hsa-miR-135a-5p/hsa-miR-23b-3p/hsa-miR-374b-5p-PTPRC/IL7R/CD69 and MALAT1-hsa-miR-135a-5p/hsa-miR-23b-3p/hsa-miR-374b-5p-IL7R/CD69 ceRNA networks were found to be related to the prognosis of SKCM. Finally, we determined the OIP5-AS1-PTPRC/IL7R/CD69 and MALAT1-IL7R/CD69 axes in ceRNA as a clinical prognostic model using correlation and Cox regression analyses. Additionally, we explored the possible role of these two axes in affecting gene expression and immune microenvironment changes and the occurrence and development of SKCM through methylation and immune infiltration analyses. In summary, the ceRNA-based OIP5-AS1-PTPRC/IL7R/CD69 and MALAT1-IL7R/CD69 axes may be a novel and important approach for the diagnosis and prognosis of SKCM.

Zhou X ，Rong R ，Xiong S ，Song W ，Ji D ，Xia X ... -  《Frontiers in Immunology》

Comprehensive analysis of the prognosis and biological significance for IFIT family in skin cutaneous melanoma.

Interferon-induced protein with tetratricopeptide repeats (IFITs) genes, consisting of four members named IFIT1, IFIT2, IFIT3 and IFIT5, are involved in the progression of multiple cancer types, but their roles in skin cutaneous melanoma (SKCM) are still largely unknown. The TCGA-SKCM dataset, GSE15605 dataset and GSE100508 dataset were obtained in our study, and multiple online databases were used for data analysis and visualization, including GEPIA, GSCALite, MethSurv, DAVID, starBase and TIMER database. The mRNA expressing levels of all the four members included in IFIT family were elevated in SKCM tissues. In addition, ROC curve showed that the combined IFITs had a higher tumor prediction performance. Kaplan-Meier survival analysis revealed that the low expression of IFIT1/2/3/5 was associated with poor overall survival (OS) and disease-specific survival (DSS) in SKCM patients. Moreover, univariate and multivariate Cox regression analysis suggested that the low expression of IFIT2/3/5 was an independent risk factor for the prognosis of SKCM patients. Besides, cancer pathway activity analysis certified that the IFITs were involved in the apoptosis pathways, epithelial-mesenchymal transition (EMT) and cell cycle. Furthermore, drug sensitivity analysis indicated that the high expression of IFIT1/2/3 was sensitive to dasatinib drug. Additionally, the expressing levels of IFITs were found to be positively correlated with the level of immune cell infiltrates, immune biomarkers and m6A regulators. Finally, using bioinformatics analysis, we predicted that PAX8-AS1/Z83843.1-miR-92a-3p-IFIT2 axis might play crucial roles in the development and progression of SKCM. This study explored the prognostic values and biological significance of the IFITs in SKCM microenvironment. IFITs may serve as novel biomarkers for the diagnosis and prognosis of melanoma and potential immunotherapeutic targets.

Jiang Y ，Zhang C ，Zhang J ，Han D ，Shi X ... -  《-》

Identification of plasma miR-4505, miR-4743-5p and miR-4750-3p as novel diagnostic biomarkers for coronary artery disease in patients with type 2 diabetes mellitus: a case-control study.

Type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) are commonly coexisting clinical entities with still growing incidence worldwide. Recently, circulating microRNAs (miRNAs) have emerged as novel molecular players in cardiometabolic diseases. This study aimed to identify a specific miRNA signature as a candidate biomarker for CAD in T2DM and to delineate potential miRNA-dependent mechanisms contributing to diabetic atherosclerosis. A total of 38 plasma samples from T2DM patients with and without CAD, CAD patients and healthy controls were collected for expression profiling of 2,578 miRNAs using microarrays. To investigate the regulatory role of differentially expressed (DE)-miRNA target genes, functional annotation and pathway enrichment analyses were performed utilizing multiple bioinformatics tools. Then, protein-protein interaction networks were established leveraging the STRING database in Cytoscape software, followed by cluster analysis and hub gene identification. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was carried out for microarray data validation in the larger replication cohort of 94 participants. Receiver operating characteristic analysis was applied to evaluate the diagnostic values of miRNAs. Multivariate logistic regression analysis was used to develop miRNA-based diagnostic models. In the discovery stage, overexpression of hsa-miR-4505, hsa-miR-4743-5p, hsa-miR-6846-5p, and down-regulation of hsa-miR-3613-3p, hsa-miR-4668-5p, hsa-miR-4706, hsa-miR-6511b-5p, hsa-miR-6750-5p, hsa-miR-4750-3p, hsa-miR-320e, hsa-miR-4717-3p, hsa-miR-7850-5p were detected in T2DM-CAD patients. The DE-miRNA target genes were significantly enriched in calcium ion binding, regulation of actin cytoskeleton, and gene expression. hsa-miR-4505, hsa-miR-4743-5p, and hsa-miR-4750-3p were found to be involved in fatty acid metabolism, leukocyte transendothelial migration, and neurotrophin signaling pathway. Dysregulation of hsa-miR-4505, hsa-miR-4743-5p, and hsa-miR-4750-3p in T2DM-CAD patients compared with T2DM subjects and controls (all p < 0.001) was further confirmed by RT-qPCR. All validated miRNAs demonstrated good discriminatory values for T2DM-CAD (AUC = 0.833-0.876). The best performance in detecting CAD in T2DM was achieved for a combination of three miRNAs (AUC = 0.959, 100% sensitivity, 86.67% specificity). Our study revealed a unique profile of plasma-derived miRNAs in T2DM patients with CAD. Potential miRNA-regulated pathways were also identified, exploring the underlying pathogenesis of CAD in T2DM. We developed a specific three-miRNA panel of hsa-miR-4505, hsa-miR-4743-5p and hsa-miR-4750-3p, that could serve as a novel non-invasive biomarker for CAD in patients with T2DM.

Szydełko J ，Czop M ，Petniak A ，Lenart-Lipińska M ，Kocki J ，Zapolski T ，Matyjaszek-Matuszek B ... -  《Cardiovascular Diabetology》

Integrated Analysis of Competing Endogenous RNAs Network Reveals Potential Signatures in Osteosarcoma Development.

Heng L ，Jia Z ，Sun J ，Zhao Y ，Zhang K ，Zhu Y ，Lu S ... -  《-》