Kidney fibrosis: from mechanisms to therapeutic medicines

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 17, 2023

Abstract Chronic kidney disease (CKD) is estimated to affect 10–14% of global population. Kidney fibrosis, characterized by excessive extracellular matrix deposition leading scarring, a hallmark manifestation in different progressive CKD; However, at present no antifibrotic therapies against CKD exist. fibrosis identified tubule atrophy, interstitial chronic inflammation and fibrogenesis, glomerulosclerosis, vascular rarefaction. Fibrotic niche, where organ initiates, complex interplay between injured parenchyma (like tubular cells) multiple non-parenchymal cell lineages (immune mesenchymal located spatially within scarring areas. Although the mechanisms are complicated due kinds cells involved, with help single-cell technology, many key questions have been explored, such as what kind renal tubules profibrotic, myofibroblasts originate, which immune how communicate each other. In addition, genetics epigenetics deeper that regulate fibrosis. And reversible nature epigenetic changes including DNA methylation, RNA interference, chromatin remodeling, gives an opportunity stop or reverse therapeutic strategies. More marketed (e.g., RAS blockage, SGLT2 inhibitors) developed delay progression recent years. Furthermore, better understanding also favored discover biomarkers fibrotic injury. review, we update advances mechanism summarize novel treatment for CKD.

Language: Английский

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The function and mechanisms of action of circular RNAs in Urologic Cancer

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 25, 2023

Abstract Kidney, bladder, and prostate cancer are the three major tumor types of urologic system that seriously threaten human health. Circular RNAs (CircRNAs), special non-coding with a stabile structure unique back-splicing loop-forming ability, have received recent scientific attention. CircRNAs widely distributed within body, important biologic functions such as sponges for microRNAs, RNA binding proteins, templates regulation transcription protein translation. The abnormal expression circRNAs in vivo is significantly associated development tumors. now emerged potential biomarkers diagnosis prognosis tumors, well targets new therapies. Although we gained better understanding circRNA, there still many questions to be answered. In this review, summarize properties detail their function, focusing on effects circRNA proliferation, metastasis, apoptosis, metabolism, drug resistance kidney, cancers.

Language: Английский

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LncRNADisease v3.0: an updated database of long non-coding RNA-associated diseases

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 52(D1), P. D1365 - D1369

Published: Oct. 11, 2023

Abstract Systematic integration of lncRNA-disease associations is great importance for further understanding their underlying molecular mechanisms and exploring lncRNA-based biomarkers therapeutics. The database long non-coding RNA-associated diseases (LncRNADisease) designed the above purpose. Here, an updated version (LncRNADisease v3.0) has curated comprehensive lncRNA (including circRNA) disease from burgeoning literatures. LncRNADisease v3.0 exhibits over 2-fold increase in experimentally supported associations, with a total 25440 entries, compared to last version. Besides, each pair assigned confidence score based on experimental evidence. Moreover, all between lncRNAs/circRNAs are classified into general causal representing whether lncRNAs or circRNAs can directly lead development progression corresponding diseases, 15721 9719 respectively. In case study, we used data calculate phenotypic similarity human mouse lncRNAs. This will continue serve as valuable resource potential clinical applications related circRNAs. freely available at http://www.rnanut.net/lncrnadisease.

Language: Английский

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EIF4A3-mediated biogenesis of circSTX6 promotes bladder cancer metastasis and cisplatin resistance

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: Jan. 2, 2024

Abstract Background Cisplatin (CDDP)-based chemotherapy is a standard first-line treatment for metastatic bladder cancer (BCa) patients, and chemoresistance remains major challenge in clinical practice. Circular RNAs (circRNAs) have emerged as essential regulators carcinogenesis progression. However, the role of circRNAs mediating CDDP chemosensitivity has yet to be well elucidated BCa. Methods CircSTX6 ( hsa_circ_0007905 ) was identified by mining public circRNA datasets verified Sanger sequencing, agarose gel electrophoresis, RNase R qRT-PCR assays. Then, function experiments were performed evaluate effects circSTX6 on BCa metastasis. Luciferase reporter assay, RNA pull-down, immunoprecipitation (RIP), stability Fluorescence situ hybridization (FISH) Immunofluorescence (IF) conducted interaction among , miR-515-3p PABPC1 SUZ12 . Animal explore tumor metastasis sensitivity. Results We that significantly upregulated samples cells Functionally, promoted cell migration invasion both vitro vivo Mechanistically, could act sponge abolish its effect Moreover, confirmed increase mRNA interacting with stabilizer subsequently promote expression SUZ12. Importantly, silencing improved CDDP-resistant CDDP. Furthermore, analysis supported knockdown attenuated resistance tumors. Conclusion These studies demonstrate plays pivotal chemoresistance, potential serve therapeutic target

Language: Английский

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The therapeutic potential of circular RNAs

Nature Reviews Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Language: Английский

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circASAP1 induces renal clear cell carcinoma ferroptosis by binding to HNRNPC and thereby regulating GPX4

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 2, 2025

Clear cell renal carcinoma (ccRCC) represents the most prevalent subtype, accounting for nearly 80% of all RCC cases. Recent research has shown that high expression circular non-coding RNA (circRNA) is associated with poor prognosis in patients clear (ccRCC), however, underlying mechanism remains unclear. After analysing self-sequenced cancer and paracancer circRNA sequencing data comparing it GEO public database, we discovered circASAP1 was significantly up-regulated cancers. We also tested levels 102 found metastasis. The interaction between circASAP1, HNRNPC their downstream target genes confirmed through experiments such as pull-down, RIP fluorescence situ hybridisation. A series vitro vivo functional were performed to verify effects on proliferation Circular analysis revealed markedly elevated ccRCC, a significant association observed Actinomycin D, RNase R, well hybridization (FISH) analyses ring structure cytoplasmic localization circASAP1. High ccRCC proliferative viability, invasion, metastasis CCK-8, transwell, plate cloning, EdU experiments. Interaction by immunoprecipitation, FISH, silver staining, mass spectrometry. Experiments using truncated isoforms demonstrated amino acids 16–87 bound Proteins altered enriched ferroptosis pathway Kyoto Encyclopedia Genes Genomes enrichment analysis. relationship ASAP1/HNRNPC/GPX4 axis experimental data, which further rescue influenced tumor growth animal predicted ccRCC. circASAP1/HNRNPC/GPX4 provides novel directions potential targets treatment.

Language: Английский

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A Smart Nano‐Theranostic Platform Based on Dual‐microRNAs Guided Self‐Feedback Tetrahedral Entropy‐Driven DNA Circuit

Advanced Science, Journal Year: 2023, Volume and Issue: 10(19)

Published: April 21, 2023

MicroRNAs (miRNAs) can act as oncogenes or tumor suppressors, capable of up down-regulating gene expression during tumorigenesis; they are diagnostic biomarkers therapeutic targets for tumors. To detect low abundance intracellular oncogenic miRNAs (onco-miRNAs) and realize synergistic therapy onco-miRNAs a smart nano-theranostic platform based on dual-miRNAs guided self-feedback tetrahedral entropy-driven DNA circuit is created. The delivery vehicle framework, in which the achieves self-feedback, between an situ amplification activation suppressor release. test this platform, selected, miRNA-155, up-regulated miRNA, cancer indicators, miRNA-122, down-regulated miRNA hepatocellular carcinoma, respectively. Through circuit, to at femtomolar level well visualized inside cells, fixed tissues, mice programmed. Furthermore, triggered by preloaded miRNA-122 amplified via released into target cells; sudden increase simultaneous decrease miRNA-155 synergistically served drugs regulation with enhanced antitumor efficacy superior biosafety. It envisioned that will initiate essential step toward theranostics personalized/precise medicine.

Language: Английский

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Extracellular vesicle-circEHD2 promotes the progression of renal cell carcinoma by activating cancer-associated fibroblasts

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: July 22, 2023

Abstract Background The encapsulation of circular RNAs (circRNAs) into extracellular vesicles (EVs) enables their involvement in intercellular communication and exerts an influence on the malignant advancement various tumors. However, regulatory role EVs-circRNA renal cell carcinoma (RCC) remains elusive. Methods vitro vivo functional experiments were implemented to measure effects circEHD2 phenotype RCC. EVs-circEHD2 activation fibroblasts was assessed by collagen contraction assay, western blotting, enzyme-linked immunosorbent assay (ELISA). mechanism investigated RNA pull-down immunoprecipitation, chromatin isolation purification, luciferase co-immunoprecipitation assay. Results We demonstrated that upregulated RCC tissues serum EVs patients with metastasis. Silencing inhibited tumor growth vivo. Mechanistic studies indicated FUS -binding protein (FUS) accelerated cyclization circEHD2, then interacts tyrosine 3-monooxygenase/tryptophan 5-monooxygenase eta (YWHAH), which acts as a bridge recruit Yes1-associated transcriptional regulator (YAP) promoter SRY-box transcription factor 9 (SOX9); this results sustained SOX9. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) regulates package EVs, transmits fibroblasts, converting cancer-associated (CAFs). Activated CAFs promote metastasis secreting pro-inflammatory cytokines such IL-6. Furthermore, antisense oligonucleotides (ASOs) targeting exhibited strong inhibition Conclusions circEHD2/YWHAH/YAP/SOX9 signaling pathway accelerates facilitates CAFs. Our suggest may be useful biomarker therapeutic target for

Language: Английский

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Likelihood-based feature representation learning combined with neighborhood information for predicting circRNA–miRNA associations

Briefings in Bioinformatics, Journal Year: 2024, Volume and Issue: 25(2)

Published: Jan. 22, 2024

Connections between circular RNAs (circRNAs) and microRNAs (miRNAs) assume a pivotal position in the onset, evolution, diagnosis treatment of diseases tumors. Selecting most potential circRNA-related miRNAs taking advantage them as biological markers or drug targets could be conducive to dealing with complex human through preventive strategies, diagnostic procedures therapeutic approaches. Compared traditional experiments, leveraging computational models integrate diverse data order infer associations proves more efficient cost-effective approach. This paper developed model Convolutional Autoencoder for CircRNA-MiRNA Associations (CA-CMA) prediction. Initially, this merged natural language characteristics circRNA miRNA sequence features circRNA-miRNA interactions. Subsequently, it utilized all pairs construct molecular association network, which was then fine-tuned by labeled samples optimize network parameters. Finally, prediction outcome is obtained utilizing deep neural networks classifier. innovatively combines likelihood objective that preserves neighborhood optimization, learn continuous feature representation words preserve spatial information two-dimensional signals. During process 5-fold cross-validation, CA-CMA exhibited exceptional performance compared numerous prior approaches, evidenced its mean area under receiver operating characteristic curve 0.9138 minimal SD 0.0024. Furthermore, recent literature has confirmed accuracy 25 out top 30 identified highest scores during case studies. The results these experiments highlight robustness versatility our model.

Language: Английский

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CircNSD1 promotes cardiac fibrosis through targeting the miR-429-3p/SULF1/Wnt/β-catenin signaling pathway

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: 45(10), P. 2092 - 2106

Published: May 17, 2024

Language: Английский

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