The role of human ribonuclease A family in health and diseases: A systematic review

Sun, Desen; Han, Chenjie; Sheng, Jinghao

doi:10.1016/j.isci.2022.105284

Cited by 14 publications

(6 citation statements)

References 118 publications

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“…Ribonuclease A family member 1 (RNASE1) is one of the best-characterized vertebrate-specific proteins that can regulate intracellular or extracellular RNA metabolism, antiviral, antibacterial, and antifungal activities, neurotoxicity, promotion of cell proliferation, anti-apoptosis, and immune regulatory abilities. RNASEs have been found to be involved in the pathogenesis of many diseases, such as infection, immune dysfunction, neurodegeneration, cancer, and cardiovascular disease ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of the immune-associated characteristics and predictive biomarkers of keratoconus based on single-cell RNA-sequencing and bulk RNA-sequencing

Niu,

Xu,

Zhu

et al. 2023

Front. Immunol.

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BackgroundWhether keratoconus (KC) is an inflammatory disease is currently debated. Hence, we aimed to investigate the immune-related features of KC based on single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data.MethodsscRNA-seq data were obtained from the Genome Sequence Archive (GSA), bulk RNA-seq data were obtained from the Gene Expression Omnibus (GEO), and immune-associated genes(IAGs) were obtained from the ImmPort database. Cell clusters of KC were annotated, and different cell clusters were then selected. The IAG score of each cell was calculated using the AUCell package. Three bulk RNA-seq datasets were merged and used to identify the differentially expressed genes (DEGs), biological functions, and immune characteristics. Weighted gene coexpression network analysis (WGCNA) was used to select the IAG score-related hub genes. Based on scRNA-seq and bulk RNA-seq analyses, three machine learning algorithms, including random forest (RF), support vector machine (SVM), and least absolute shrinkage and selection operator (LASSO) regression analysis, were used to identify potential prognostic markers for KC. A predictive nomogram was developed based on prognostic markers.ResultsSix cell clusters were identified in KC, and decreased corneal stromal cell-5 (CSC-5) and increased CSC-6 were found in KC. CSC and immune cell clusters had the highest IAG scores. The bulk RNA-seq analysis identified 1362 DEGs (553 upregulated and 809 downregulated) in KC. We found different immune cell populations and differentially expressed cytokines in KC. More than three key IAG score-related modules and 367 genes were identified. By integrating the scRNA-seq and bulk RNA-seq analyses, 250 IAGs were selected and then incorporated into three machine learning models, and 10 IAGs (CEP112, FYN, IFITM1, IGFBP5, LPIN2, MAP1B, RNASE1, RUNX3, SMIM10, and SRGN) were identified as potential prognostic genes that were significantly associated with cytokine and matrix metalloproteinase(MMP)1-14 expression. Finally, a predictive nomogram was constructed and validated.ConclusionTaken together, our results identified CSCs and immune cell clusters that may play a key role during KC progression by regulating immunological features and maintaining cell stability.

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Section: Discussionmentioning

confidence: 99%

Identification of the immune-associated characteristics and predictive biomarkers of keratoconus based on single-cell RNA-sequencing and bulk RNA-sequencing

Niu,

Xu,

Zhu

et al. 2023

Front. Immunol.

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“…Thus, the modulation of human RNases with small molecules has been studied as a promising strategy for developing therapeutics and various biological applications. For example, RNase A family ribonucleases RNase 1 and Angiogenin are secretory enzymes involved in host defense, tightly regulated by RNase inhibitor protein. , First reported RNase A family inhibitors were derived from nucleotide structures and showed nanomolar activities, followed by a few small-molecule inhibitors with moderate activities. − …”

Section: Small Molecules Targeting Human Ribonucleasesmentioning

confidence: 99%

“…For example, RNase A family ribonucleases RNase 1 and Angiogenin are secretory enzymes involved in host defense, tightly regulated by RNase inhibitor protein. 65 , 66 First reported RNase A family inhibitors were derived from nucleotide structures and showed nanomolar activities, followed by a few small-molecule inhibitors with moderate activities. 67 − 69 …”

Section: Small Molecules Targeting Human Ribonucleasesmentioning

confidence: 99%

Targeting Ribonucleases with Small Molecules and Bifunctional Molecules

Borgelt

2023

ACS Chem. Biol.

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Ribonucleases (RNases) cleave and process RNAs, thereby regulating the biogenesis, metabolism, and degradation of coding and noncoding RNAs. Thus, small molecules targeting RNases have the potential to perturb RNA biology, and RNases have been studied as therapeutic targets of antibiotics, antivirals, and agents for autoimmune diseases and cancers. Additionally, the recent advances in chemically induced proximity approaches have led to the discovery of bifunctional molecules that target RNases to achieve RNA degradation or inhibit RNA processing. Here, we summarize the efforts that have been made to discover small-molecule inhibitors and activators targeting bacterial, viral, and human RNases. We also highlight the emerging examples of RNase-targeting bifunctional molecules and discuss the trends in developing such molecules for both biological and therapeutic applications.

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“…3,4 For instance, monoclonal antibodies targeting specific proteins on cancer cells can effectively block or modulate cancerpromoting signals, leading to improved patient outcomes. 5,6 Ribonuclease A (RNase A) is a naturally occurring protein that has gained significant attention in the field of protein therapy, [7][8][9] as it can specifically recognize and bind to the abnormal RNA structure and further cleave the dysregulated RNA molecules to induce the apoptosis of cancer cells. 10 Thus, RNase A possesses selective cytotoxicity towards cancer cells while sparing normal cells, making it an attractive candidate for targeted cancer therapy.…”

Section: Introductionmentioning

confidence: 99%