Identification and validation of shared gene signature of kidney renal clear cell carcinoma and COVID-19.

Background: COVID-19 is a severe infectious disease caused by the SARS-CoV-2 virus, and previous studies have shown that patients with kidney renal clear cell carcinoma (KIRC) are more susceptible to SARS-CoV-2 infection than the general population. Nevertheless, their co-pathogenesis remains incompletely elucidated. Methods: We obtained shared genes between these two diseases based on public datasets, constructed a prognostic risk model consisting of hub genes, and validated the accuracy of the model using internal and external validation sets. We further analyzed the immune landscape of the prognostic risk model, investigated the biological functions of the hub genes, and detected their expression in renal cell carcinoma cells using qPCR. Finally, we searched the candidate drugs associated with hub gene-related targets from DSigDB and CellMiner databases. Results: We obtained 156 shared genes between KIRC and COVID-19 and constructed a prognostic risk model consisting of four hub genes. Both shared genes and hub genes were highly enriched in immune-related functions and pathways. Hub genes were significantly overexpressed in COVID-19 and KIRC. ROC curves, nomograms, etc., showed the reliability and robustness of the risk model, which was validated in both internal and external datasets. Moreover, patients in the high-risk group showed a higher proportion of immune cells, higher expression of immune checkpoint genes, and more active immune-related functions. Finally, we identified promising drugs for COVID-19 and KIRC, such as etoposide, fulvestrant, and topotecan. Conclusion: This study identified and validated four shared genes for KIRC and COVID-19. These genes are associated with immune functions and may serve as potential prognostic biomarkers for KIRC. The shared pathways and genes may provide new insights for further mechanistic research and treatment of comorbidities.

Preliminary study on the role of the CSMD2 gene in bladder cancer.

Background: CSMD2 has been reported as a potential prognostic factor in several cancers. However, whether CSMD2 affects bladder cancer (BC) remains unclear. Methods: Public data were obtained from the TCGA (https://cancergenome.nih.gov) databases. CSMD2expression and its prognostic value were analyzed using bioinformatics methods. CSMD2 mRNA level in patients with BC and BC cell lines was evaluated via quantitative reverse transcriptase polymerase chain reaction. CSMD2 protein level in patients with BC was evaluated via immunohistochemistry. BC cell lines T24 and UMUC-3 were selected for loss-of-function assays targeting CSMD2. Cell viability was determined by CCK8 and clone formation experiments. Cell migration and invasion were evaluated using Transwell assays. Furthermore, the transcriptome of UMUC-3 with CSMD2 knockdown was sequenced to analyze potential signaling network pathways. Finally, the TIMER2.0 database was employed to identify the correlation between CSMD2 and immune cells in the tumor microenvironment. Results: CSMD2 expression was up-regulated in BC tissues compared to adjacent tissues. High CSMD2 expression was associated with poor survival and could serve as an independent predictor for survival in patients with BC. Furthermore, down-regulation of CSMD2 notably restrained the viability, migration, and invasion abilities of T24 and UMUC-3 cells. Moreover, transcriptomic sequencing after CSMD2 knockdown in UMUC-3 cells revealed its involvement in the regulation of the malignant phenotype in BC. Finally, public databases suggest a connection between CSMD2 and immune cell infiltration in BC. Conclusions: These findings suggest that CSMD2 may promote proliferation and tumorigenicity, and could represent a potential target for improving the prognosis of BC.

CircFSCN1 induces tumor progression and triggers epithelial-mesenchymal transition in bladder cancer through augmentation of MDM2-mediated p53 silencing.

BACKGROUND: Compelling evidences indicated that circular RNA (circRNA) was a novel class of non-coding RNA that played critical and distinct roles in various human cancers. Their roles and underlying mechanisms, however, in bladder cancer (BC) remained largely unknown. METHODS: A novel circRNA derived from oncogene FSCN1, namely circFSCN1, was selected from a microarray analysis. The phenotypic alterations were assessed with functional experiments in vitro and in vivo. RNA immunoprecipitation, RNA pull-down, luciferase reporter assay, and rescue experiments were sequentially proceeded to clarify the interactions among circFSCN1, miR-145-5p, MDM2, and p53. RESULTS: We observed that the expression of circFSCN1 was elevated in BC cell lines and tissues. Next, we validated the fundamental properties of circFSCN1. In the meanwhile, we noticed that elevated circFSCN1 level, pathological T stage, and tumor grade were identified as independent factors associated with cancer-specific survivals of patients with BC，as determined by univariate and multivariable COX regression analyses. Phenotype studies demonstrated the promoting effects of circFSCN1 on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of BC cells. Mechanistically, we elucidated that circFSCN1, primarily localized in the cytoplasm, upregulated the expression of MDM2, a well-known inhibitor of p53, by directly binding to miR-145-5p. CONCLUSIONS: Elevated circFSCN1 induces tumor progression and EMT in BC via enhancing MDM2-mediated silencing of p53 by sponging miR-145-5p. Targeting circFSCN1, a novel identified target, may be conducive in impeding BC progression and providing survival benefits for patients with BC.

Transcriptome sequencing and single-cell sequencing analysis identify GARS1 as a potential prognostic and immunotherapeutic biomarker for multiple cancers, including bladder cancer.

Background: Glycyl-tRNA synthetase 1 (GARS1) belongs to the aminoacyl-tRNA synthetase family, playing a crucial role in protein synthesis. Previous studies have reported a close association between GARS1 and various tumors. However, the role of GARS1 in human cancer prognosis and its impact on immunology remain largely unexplored. Methods: In this study, we comprehensively analyzed GARS1 expression at the mRNA and protein levels, examined genetic alterations, and assessed its prognostic implications in pan-cancer, with a specific emphasis on the immune landscape. Furthermore, we investigated the functional enrichment of genes related to GARS1 and explored its biological functions using single-cell data. Finally, we conducted cellular experiments to validate the biological significance of GARS1 in bladder cancer cells. Results: In general, GARS1 expression was significantly upregulated across multiple cancer types, and it demonstrated prognostic value in various cancers. Gene Set Enrichment Analysis (GSEA) revealed the association of GARS1 expression with multiple immune regulatory pathways. Moreover, GARS1 exhibited significant correlations with immune infiltrating cells (such as DC, CD8+T cells, Neutrophils, and Macrophages), immune checkpoint genes (CD274, CD276), and immune regulatory factors in tumors. Additionally, we observed that GARS1 could effectively predict the response to anti-PD-L1 therapy. Notably, Ifosfamide, auranofin, DMAPT, and A-1331852 emerged as potential therapeutic agents for GARS1-upregulated tumors. Our experimental findings strongly suggest that GARS1 promotes the proliferation and migration of bladder cancer cells. Conclusion: GARS1 holds promise as a potential prognostic marker and therapeutic target for pan-cancer immunotherapy, offering valuable insights for the development of more precise and personalized approaches to tumor treatment in the future.

Prognostic biomarker DARS2 correlated with immune infiltrates in bladder tumor.

Background: DARS2 is a pivotal member of the Aminoacyl-tRNA synthetases family that is critical for regulating protein translation. However, the biological role of DARS2 in bladder cancer remains elusive. Methods: We analyzed the correlation between DARS2 expression and prognosis, tumor stage, and immune infiltration in bladder cancer using The Cancer Genome Atlas (TCGA) database. We validated findings in clinical samples from The First Affiliated Hospital of Nanchang University and explored the biological functions of DARS2 using cell and animal models. Results: We found DARS2 to be upregulated in bladder cancer, associated with tumor progression and poor prognosis. Immune infiltration analysis suggested that DARS2 may facilitate immune evasion by modulating PD-L1. Cell and animal experiments validated that DARS2 knockdown and overexpress can inhibit or increase cancer cell proliferation, metastasis, tumorigenesis, immune escape, and PD-L1 levels. Conclusions: Our study reveals DARS2 as a potential prognostic biomarker and immunotherapy target in BLCA.

Removal of Heavy Metals from Acid Mine Drainage by Red Mud-Based Geopolymer Pervious Concrete: Batch and Long-Term Column Studies.

Various metal ions in acid mine drainage (AMD) cause environmental pollution. Due to the unique advantages of heavy metal treatment and gelling properties, previous concretes incorporating red mud have attracted extensive attention in AMD passive treatment, which utilises naturally occurring chemicals to cleanse contaminated mine waters with low operating costs. This study aims to develop red mud-based geopolymer pervious concrete as an eco-friendly method to remove heavy metals in AMD. Compared with raw pervious concrete, red mud-based geopolymer pervious concrete improves the purification efficiency of heavy metals. The high rate of acid reduction and metal removal by the geopolymer is attributed to the dissolution of portlandite in red mud. Precipitation of metal hydroxides seems to be the dominant metal removal mechanism. Under optimal conditions (influent pH = 4.0 and the hydraulic retention time = 24 h), red mud-based geopolymer pervious concrete could completely remove Cu(II), Mn(II), Cd(II) and Zn(II) by up to 10 mg/L, 10 mg/L, 1.6 mg/L and 16 mg/L, respectively. When the influent pH is 2.5, the hydrolysis of Fe(III) released from red mud increases the consumption of OH-. Moreover, when the influent pH is 4.0, the precipitation of CaSO4 promotes the dissolution of portlandite and metal removal. Therefore, red mud has demonstrated feasibility in the manufacturing of geopolymer-based pervious concrete for purification AMD.