The role of miR-200 family in the regulation of hallmarks of cancer

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Sept. 8, 2022

MiRNAs are short non-coding RNAs that regulate gene expression post-transcriptionally contributing to the development of different diseases including cancer. The miR-200 family consists five members, miR-200a, miR-200b, miR-200c, miR-141, and miR-429. Their is dysregulated in cancer tissue their level altered body fluids patients. Moreover, levels members correlate with clinical parameters such as patients’ survival which makes them potentially useful diagnostic prognostic biomarkers. can act either oncomiRs or tumor suppressor miRNAs depending on target genes role regulation key oncogenic signaling pathways. In most types cancer, acts miRNA regulates all features this review, we summarized pattern potential utility comprehensively described hallmarks proposed by Hanahan Weinberg focus epithelial-mesenchymal transition, invasiveness, metastasis cells.

Language: Английский

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Ubiquitination Links DNA Damage and Repair Signaling to Cancer Metabolism

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8441 - 8441

Published: May 8, 2023

Changes in the DNA damage response (DDR) and cellular metabolism are two important factors that allow cancer cells to proliferate. DDR is a set of events which recognized, repair recruited site damage, lesion repaired, responses associated with processed. In cancer, commonly dysregulated, enzymes prone changes ubiquitination. Additionally, metabolism, especially glycolysis, upregulated cells, this metabolic pathway modulated by The ubiquitin-proteasome system (UPS), particularly E3 ligases, act as bridge between since they regulate processes. Hence, ligases high substrate specificity considered potential therapeutic targets for treating cancer. A number small molecule inhibitors designed target different components UPS have been developed, several tested clinical trials human use. review, we discuss role ubiquitination on overall confirm link them through NEDD4, APC/CCDH1, FBXW7, Pellino1. addition, present an overview clinically implications their practical

Language: Английский

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Pharmacological impact of microRNAs in head and neck squamous cell carcinoma: Prevailing insights on molecular pathways, diagnosis, and nanomedicine treatment

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: May 3, 2023

Head and neck squamous cell carcinoma is a disease that most commonly produce tumours from the lining of epithelial cells lips, larynx, nasopharynx, mouth, or oro-pharynx. It one deadly forms cancer. About to two percent all neo-plasm-related deaths are attributed head carcinoma, which responsible for about six cancers. MicroRNAs play critical role in proliferation, differentiation, tumorigenesis, stress response, triggering apoptosis, other physiological process. regulate gene expression provide new diagnostic, prognostic, therapeutic options carcinoma. In this work, molecular signaling pathways related emphasized. We also an overview MicroRNA downregulation overexpression its as diagnostic prognostic marker recent years, nano-based therapies have been explored. addition, nanotechnology-based alternatives discussed promising strategy exploring paradigms aimed at improving efficacy conventional cytotoxic chemotherapeutic agents against attenuating their cytotoxicity. This article provides information on ongoing recently completed clinical trials based nanotechnology.

Language: Английский

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Modelling radiobiology

Physics in Medicine and Biology, Journal Year: 2024, Volume and Issue: 69(18), P. 18TR01 - 18TR01

Published: Aug. 19, 2024

Radiotherapy has played an essential role in cancer treatment for over a century, and remains one of the best-studied methods treatment. Because its close links with physical sciences, it been subject extensive quantitative mathematical modelling, but complete understanding mechanisms radiotherapy remained elusive. In part this is because complexity range scales involved radiotherapy-from radiation interactions occurring nanometres to evolution patient responses months years. This review presents current status ongoing research modelling across these scales, including basic DNA damage, immediate biological triggers, genetic- patient-level determinants response. Finally, some major challenges field potential avenues future improvements are also discussed.

Language: Английский

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High-throughput 3D Spheroid Screens Identify microRNA Sensitizers for Improved Thermoradiotherapy in Locally Advanced Cancers

Molecular Therapy — Nucleic Acids, Journal Year: 2025, Volume and Issue: 36(2), P. 102500 - 102500

Published: March 5, 2025

Chemoradiotherapy is the standard of care for many locally advanced cancers, including cervical and head neck but patients cannot tolerate chemotherapy. Clinical trials have shown that radiotherapy combined with hyperthermia (thermoradiotherapy) may be equally effective, yet it yields a suboptimal overall survival patients, emphasizing need improvement. MicroRNAs (miRNAs), short non-coding RNA sequences, are often dysregulated in cancer exhibit significant potential as radiosensitizers by targeting genes associated DNA damage response. In this study, high-throughput miRNA screening four cell lines identified 55 miRNAs sensitizing potential, 18 validated across 10 additional (6 4 neck). Functional studies 6 miRNAs, miR-16, miR-27a, miR-181c, miR-221, miR-224, miR-1293, showed they reduced repair downregulating ATM, DNA-PKcs, Ku70/80, RAD51. Additionally, differential expression miR-224 treatment-sensitive versus treatment-resistant indicated their predictive biomarker treatment response patients. Conclusively, study has promising development sensitizers thermoradiotherapy provide biomarkers predicting cancers.

Language: Английский

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Integrated bioinformatics approach for the identification and validation of novel biomarkers in ACC progression and prognosis

Biomarkers, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 21

Published: April 4, 2025

Adrenocortical carcinoma (ACC) is a rare and extremely lethal endocrine malignancy emerging from adrenal cortex, characterized by poor prognosis. This study, performed integrated bioinformatics to elucidate the underlying molecular mechanisms identify novel biomarkers, validating them as therapeutic targets for ACC The RNA-seq data across five gene expression profiles identified 79 DEGs through comparative analysis of normal specimens. Functional enrichment pathway analyses using DAVID database revealed most significant GO terms enriched KEGG pathways. PPI network was constructed utilizing STRING database, followed module in Cytoscape. Finally, 10 hub genes were including TAGLN, LUM, PDGFRA, FBLN5, MMP2, LAMA2, DCN, IGF1, FBLN1 CXCL12 potential biomarkers. Subsequent survival confirmed that FBLN5 are significantly associated with patient survivability. Furthermore, TFs-DEGs miRNAs-DEGs analyses, transcriptional post-translational regulators. gene-disease gene-drug association, highlighted correlated diseases their promising inhibitors. In conclusion, biomarkers pathways, provides comprehensive insight into mechanisms, prognosis, clinical applications diagnosis interventions ACC.

Language: Английский

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TATDN2 resolution of R-loops is required for survival of BRCA1-mutant cancer cells

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 51(22), P. 12224 - 12241

Published: Nov. 11, 2023

Abstract BRCA1-deficient cells have increased IRE1 RNase, which degrades multiple microRNAs. Reconstituting expression of one these, miR-4638–5p, resulted in synthetic lethality cancer cells. We found that miR-4638-5p represses TATDN2, a poorly characterized member the TATD nuclease family. discovered human TATDN2 has RNA 3′ exonuclease and endonuclease activity on double-stranded hairpin structures. Given cleavage by difficulty resolving R-loops, we tested whether could resolve R-loops. Using vitro biochemical reconstitution assays, bound to R-loops degraded strand but not DNA forms Mg2+-dependent manner. Mutations amino acids E593 E705 predicted Alphafold-2 chelate an essential Mg2+ cation completely abrogated this R-loop resolution activity. Depleting cellular damage chromosomal instability. Loss poor replication fork progression presence Significantly, is for survival cells, much less so cognate BRCA1-repleted Thus, propose novel target therapy cancers.

Language: Английский

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MiR-34b promotes oxidative stress and induces cellular senescence through TWIST1 in human cervical cancer

Translational Oncology, Journal Year: 2024, Volume and Issue: 48, P. 102063 - 102063

Published: Aug. 1, 2024

The aim of this research was to elucidate the role miR-34b in cervical cancer progression and underlying mechanism behind miR-34b-mediated tumor suppression. study revealed as a senescence inducer serves potential therapeutic target developing combination therapy with senotherapeutics.

Language: Английский

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Genetic and Epigenetic Biomarkers Associated with Early Relapse in Pediatric Acute Lymphoblastic Leukemia: A Focused Bioinformatics Study on DNA-Repair Genes

Biomedicines, Journal Year: 2024, Volume and Issue: 12(8), P. 1766 - 1766

Published: Aug. 5, 2024

Genomic instability is one of the main drivers tumorigenesis and development hematological malignancies. Cancer cells can remedy chemotherapeutic-induced DNA damage by upregulating DNA-repair genes ultimately inducing therapy resistance. Nevertheless, association between genes, drug resistance, disease relapse has not been well characterized in acute lymphoblastic leukemia (ALL). This study aimed to explore role machinery molecular mechanisms which it regulated early- late-relapsing pediatric ALL patients. We performed secondary data analysis on Therapeutically Applicable Research Generate Effective Treatments (TARGET)—ALL expansion phase II trial 198 relapsed precursor B-cell ALL. Comprehensive genetic epigenetic investigations 147 were conducted study. Gene expression was assessed using Microarray RNA-sequencing platforms. alternations, methylation status, miRNA transcriptome investigated for candidate genes. identified three ALKBH3, NHEJ1, PARP1, that upregulated early relapsers compared late (p < 0.05). Such upregulation at diagnosis significantly associated with disease-free survival overall precursor-B-ALL Moreover, PARP1 accompanied a significant downregulation its targeting miRNA, miR-1301-3p = 0.0152), strongly linked poorer survivals. Upregulation particular, increases likelihood children. The observation relative might serve as valid rationale proposing alternative treatment approaches, such PARP inhibitors chemotherapy.

Language: Английский

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Multiple Genetic Polymorphisms within microRNA Targets and Homologous microRNA-Binding Sites: Two More Factors Influencing microRNA-Mediated Regulation of Gene Expression

IntechOpen eBooks, Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 14, 2023

miRNA-mRNA interaction depends on multiple factors such as 3’UTR isoforms, the cell and tissue-specific expression levels of RNA-binding proteins, sequence context around mRNA target site, other mechanisms. Genetic polymorphisms within miRNAs their sites appear to be among most important ones because they influence mode outcome universally irreversibly. SNP disruption binding sites, well conformational changes preventing access miRNA its are adopted credible mechanistic explanations SNP-mediated effects. The occurrence SNPs same miRNA-binding site implies combinatorial action. presence repetitive (homologous) for may both enhance targeting provide backup instead one disrupted by SNP, thus rescuing functionality. While being underexplored, genetic homologous considered additional influencing miRNA-mediated regulation gene expression.

Language: Английский

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