Recent studies have reported the promising value of differential gene expression analysis and weighted gene coexpression network analysis (WGCNA) for identifying disease biomarkers. Based on this method, this study intends to characterize the hub genes and pathways related to retinal photoreceptor cell (PRC) injury in the context of retinitis pigmentosa (RP). A total of 53 coexpression modules were identified by WGCNA, among which lightpink4, darkolivegreen, tan4, blue2, skyblue2, and navajowhite2 ranked at the top. By analyzing the RP microarrays retrieved from the GEO database, 338 differentially expressed genes (DEGs) were identified in the RP samples. Forty-five candidate genes were selected from these DEGs by intersection with the genes in the coexpression modules. These intersection genes were subjected to GO and KEGG analyses. Furthermore, the genes and pathways involved in PRC damage were identified based on analyses utilizing GeneCards and STRING tools. Transcription factor 7-like 1 (TCF7L1, also called TCF3) was suggested to participate in the RP-associated PRC damage through the Wnt signaling pathway. It was validated in a blue light-irradiated cell model that TCF7L1 overexpression boosted PRC viability and repressed apoptosis. Inhibition of the Wnt signaling pathway also contributed to protective effects. Together, the data mentioned above supported the conclusion that either elevation of TCF7L1 or blockade of the Wnt signaling pathway could prevent RP progression by protecting PRCs from damage.

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Recent years have witnessed an increasing research interest in the therapeutic value of aberrant chromatin regulatory processes in carcinogenesis. Our study was performed to explore the possible carcinogenic mechanism of the chromatin regulator RuvB-like protein 1 (RUVBL1) in uveal melanoma (UVM). The expression pattern of RUVBL1 was retrieved in bioinformatics data. The correlation between RUVBL1 expression and the prognosis of patients with UVM was analyzed in publicly available database. The downstream target genes of RUVBL1 were predicted and further verified by co-immunoprecipitation. The bioinformatics analysis results showed that RUVBL1 may be associated with the transcriptional activity of CTNNB1 by regulating chromatin remodeling, and that RUVBL1 functioned as an independent prognostic factor for patients with UVM. The UVM cells manipulated with RUVBL1 knockdown were introduced for in vitro investigation. CCK-8 assay, flow cytometry, scratch assay, Transwell assay and Western blot analysis were used for detection on the resultant UVM cell proliferation, apoptosis, migration, invasion and cell cycle distribution. In vitro cell experimental data showed that RUVBL1 expression was significantly increased in UVM cells and RUVBL1 knockdown inhibited the proliferation, invasion and migration of UVM cells, accompanied by augmented apoptosis rate and blocked cell cycle progression. To sum up, RUVBL1 enhances the malignant biological characteristics of UVM cells by increasing the chromatin remodeling and subsequent transcription activity of CTNNB1.

Single‐cell RNA sequencing (scRNA‐seq) technologies enable the profiling and analysis of the transcriptomes of single cells and hold promise for clarifying gene mechanisms at single‐cell resolution. We based this study on scRNA‐seq data to reveal glaucoma‐related genes and downstream pathways with neuroprotection effects. The scRNA‐seq datasets related to glaucoma of retinal tissue samples of human beings and Atonal Homolog 7 (ATOH7)‐null mice were obtained from the GEO database. The 74 top marker genes and 20 cell clusters were obtained in human retinal tissue samples. The key gene ATOH7 was found after the intersection with genes from GeneCards data. In the ATOH7‐null mouse retinal tissue samples, pseudotime inference demonstrated significant changes in cell differentiation. Moreover, mouse retinal photoreceptor cells (PRCs) were cultured and treated with lentivirus carrying oe‐ATOH7 alone or in combination with Notch signaling pathway activator Jagged‐1/FC, after which cell biological functions were determined. The involvement of ATOH7 in glaucoma was identified through regulating PRCs. Furthermore, ATOH7 conferred neuroprotection in PRCs in glaucoma by mediating the Notch signaling pathway. In vitro data confirmed that ATOH7 overexpression promoted the differentiation of PRCs and inhibited their apoptosis by suppressing the Notch signaling pathway. The evidence provided by our study highlighted the involvement of ATOH7 in the blockade of the Notch signaling pathway, resulting in the neuroprotection for PRCs in glaucoma.image