MiR-138 has been shown to be downregulated in various cancers, including head and neck squamous cell carcinoma (HNSCC) and clear cell renal carcinoma (ccRCC). In the present study, we aimed to reveal the mechanism of miR-138 induction of senescence in renal carcinoma cells and identify its specific target genes. We used qRT-PCR to analyze miR-138 expression levels in renal carcinoma cell lines and ccRCC samples. The activity of β-galactosidase was measured for functional analysis after miR-138 mimic transfection. To identify the targets of miR-138, we used three types of target prediction software to determine three candidate target genes. Furthermore, a 3'UTR luciferase assay was performed. Western blotting was used to detect the protein expression levels of candidate target genes. Additionally, knockdown of EZH2 by its siRNA was performed. The expression of miR-138 was downregulated in RCC cells lines and in tumor samples compared with their controls. Transfection of miR-138 mimic induced SN-12 cell senescence, decreased the protein expression of EZH2, and increased the protein expression of P16. Furthermore, miR-138 decreased the 3'UTR luciferase activity of EZH2. The knockdown of EZH2 by siRNA induced SN-12 cell senescence, decreased the protein expression level of EZH2, and increased the protein expression of P16. MiR-138 is a tumor-suppressor miRNA in ccRCC that induces SN-12 cell senescence by downregulating EZH2 expression and upregulating P16 expression.

The aim of the present study was to investigate the changes in retinal gene expression at three time points and assess the underlying molecular mechanisms of diabetic retinopathy (DR) in a streptozotocin (STZ)-induced diabetes rat model using bioinformatics analysis. The gene expression profile of GSE28831 was extracted from the Gene Expression Omnibus database and differentially expressed genes (DEGs) were identified at three different time points (1, 4 and 12 weeks) using the limma package in R language. Gene ontology (GO) enrichment analysis of DEGs was performed followed by a principal component and pathway enrichment analysis of the selected DEGs along with protein-protein interaction network construction at the three time points. A total of 402, 105 and 213 DEGs were screened at 1, 4 and 12 weeks, respectively. In addition, the expression of 8 genes was identified to be significantly different at different time points, including cytochrome P450 2B2 (CYP2B2; downregulated gene; P=0.048; at 1 week), mannan binding lectin-associated serine protease-2 (MASP2; downregulated gene; P=0.044), lecithin retinol acyltransferase (LRAT; downregulated gene; P=0.015), retinal pigment epithelium (RPE)-specific protein 65 kDa (RPE65; downregulated gene; P=0.025), 11-cis-retinoldehydrogenase (RDH5; downregulated gene; P=0.04; at 4 weeks), mitogen-activated protein kinase 13 (MAPK13; upregulated gene; P=0.036), LRAT (downregulated gene; P=0.01) and RPE65 (downregulated gene; P=0.009; at 12 weeks). Furthermore, pathway enrichment and GO enrichment analyses revealed that DEGs at 4 weeks were primarily enriched in retinol metabolism and processes associated with visual functions, including ‘visual perception’ and ‘retinol metabolism’. DEGs, including CYP2B2, MASP2, LRAT, RPE65, RDH5 and MAPK13 may be potential targets for the diagnosis and treatment of DR. Thus, the current study demonstrated that abnormal visual functions occur at 4 weeks in STZ-induced diabetic rats. This may provide a scientific basis for the diagnosis and treatment of DR because DEGs may be used to facilitate the development of novel therapeutic strategies to diagnose and treat DR.

Objective This study aimed to identify key diagnostic markers and immune infiltration of (SONFH) by bioinformatics analysis. Methods Related SONFH datasets were downloaded from the Gene Expression Omnibus (GEO) database. First, we identified the differentially expressed genes (DEGs) and performed the functional enrichment analysis. Then weighted correlation network analysis (WGCNA) and the MCODE plug-in in Cytoscape were used to identify the diagnostic markers of SONFH. Finally, CIBERSORT was used to analyze the immune infiltration between SONFH and healthy controls, and the correlation between infiltrating immune cells and diagnostic markers was analyzed. Results TYROBP, TLR2, P2RY13, TLR8, HCK, MNDA, and NCF2 may be key diagnostic markers of SONFH. Immune cell infiltration analysis revealed that Memory B cells and activated dendritic cells may be related to the SONFH process. Moreover, HCK was negatively correlated with CD8 T cells, and neutrophils were positively correlated with those key diagnostic markers. Conclusions TYROBP, TLR2, P2RY13, TLR8, HCK, MNDA, and NCF2 may be used as diagnostic markers of SONFH, and immune-related mechanism of SONFH and the potential immunotherapy are worthy of further study.

Purpose: To investigate the specific function of long noncoding RNA FGD5 antisense RNA 1 (lncRNA FGD5-AS1) in glioma. Materials and Methods: The level of FGD5-AS1 was detected in clinical samples and cell lines by qRT-PCR. Small interfering RNA (siRNA) of FGD5-AS1 or scramble siRNA was transfected into U87 cell lines to examine the role of FGD5-AS1 on glioma development. The proliferation of glioma cells was tested by Cell Counting Kit-8 (CCK-8), the migration and invasion of glioma cells were tested by transwell assay without matrigel or with matrigel. Western blot was used to detect the protein expression, and XAV-939 was used to inhibit wnt/β-catenin pathway. The effect of FGD5-AS1 on tumorigenesis of glioma was confirmed by xenograft nude mice model. Results: FGD5-AS1 was significantly increased in glioma tissues and cells. Loss of FGD5-AS1 inhibited the proliferation, migration and invasion of U87 cells. Furthermore, overexpression of FGD5-AS1 increased the mRNA and protein levels of β-catenin and cyclin D1. Blocking of wnt/β-catenin using XAV-939 reversed the promotion role of FGD3-AS1 on glioma cells' migration and invasion. The in vivo tumor growth assay showed that FGD3-AS1 accelerated glioma tumorigenesis with activating wnt/β-catenin pathway. Conclusion: Our research emphasized FGD5-AS1 acting as an oncogene by regulating wnt/ β-catenin signaling pathway, thus providing some novel experimental basis for clinical treatment of glioma.