Multi-target therapeutic modulation with natural compounds towards DNA repair MRN-checkpoint sensor genes (MRN-CSGs) and oncogenic miRNAs in breast cancer patients: a Clinico-Informatic study DOI
Jitender Singh,

K.L. Khanduja,

Pramod Avti

et al.

Integrative Biology, Journal Year: 2024, Volume and Issue: 16

Published: Jan. 1, 2024

Abstract Breast cancer, more prevalent in women, often arises due to abnormalities the MRN-checkpoint sensor genes (MRN-CSG), responsible for DNA damage detection and repair. Abnormality this complex is suppression of various effectors such as siRNAs, miRNAs, transcriptional factors breast tumor progression. This study analyzed samples (n = 60) identified four common miRNAs (miR-1-3p, miR-210-3p, miR-16-5p, miR-34a-5p) out 12, exploring their interactions with MRN-CSG. The 3D structures these miRNA-MRN-CSG complexes displayed strong thermodynamic stability. Screening 7711 natural compounds resulted two (F0870–0001 F0922–0471) lowest ligand binding energies (ΔG −8.4 to−11.6 kcal/mol), targeting miRNAs. Docking results showed that one compound (PubChem id-5 281 614) bound all MRN-CSG components −6.2 −7.3 while F6782–0723 only RAD50 NBN. These exhibited minimal dissociation constants (Kd Ki) thermodynamically stable minimum free energy (MMGBSA) values. Molecular dynamics simulations indicated highly compound-MRN-CSG complexes, consistent RMSD, RMSF, residual correlation. top-selected robust intermolecular H-bonding, low carcinogenicity, toxicity, drug-like properties. Consequently, hold promise regulating miRNA repair mechanisms cancer therapy. Insight Box: investigated interact crucial highlighted −11.6 (miR-1-3p miR-34a-5p). Another 614, ΔG kcal/mol) components, targeted stability, favorable MMGBSA values, constants. confirmed stability properties compounds, indicating potential therapy by modulating mechanisms.

Language: Английский

MicroRNAs as Endocrine Modulators of Breast Cancer DOI Open Access
Vinitha Richard, Kevin Lee,

Michael Joseph Kerin

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3449 - 3449

Published: April 7, 2025

Breast cancer is an aggressive disease of multiple subtypes with varying phenotypic, hormonal, and clinicopathological features, offering enhanced resistance to conventional therapeutic regimens. There unmet need for reliable molecular biomarkers capable detecting the malignant transformation from early stages enhance diagnosis treatment outcomes. A subset small non-coding nucleic acid molecules, micro ribonucleic acids (microRNAs/miRNAs), have emerged as promising due their role in gene regulation pathogenesis. This review discusses, detail, different origins hormone-like regulatory functionalities miRNAs localized tumor tissue circulation, well inherent stability turnover that determines utility detection, monitoring, prognosis, targets.

Language: Английский

Citations

0
Clinical implications of miR-195 in cancer: mechanisms, potential applications, and therapeutic strategies DOI Creative Commons

Shuli Xu,

Lan He,

Yan Chen

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2025, Volume and Issue: 151(4)

Published: April 22, 2025

Language: Английский

Citations

0
Integrated miRNA Signatures: Advancing Breast Cancer Diagnosis and Prognosis DOI Creative Commons
Μαρία Σαμαρά, Eleni Thodou,

Marina Patoulioti

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(11), P. 1352 - 1352

Published: Oct. 24, 2024

Breast cancer ranks first in incidence and second deaths worldwide, presenting alarmingly rising mortality rates. Imaging methodologies and/or invasive biopsies are routinely used for screening detection, although not always with high sensitivity/specificity. MicroRNAs (miRNAs) could serve as diagnostic prognostic biomarkers breast cancer. We have designed a computational approach combining transcriptome profiling, survival analyses, power calculations from 1165 patients carcinoma The Cancer Genome Atlas (TCGA-BRCA). Our strategy yielded two separate miRNA signatures consisting of four up-regulated five down-regulated miRNAs tumors, cumulative strength AUC 0.93 0.92, respectively. provide direct evidence regarding the cancer-specific expression both through multicancer comparison >7000 representing 19 solid types, challenging their potency beyond any current methods. functionally implicated cancer-related processes statistically significant effects on overall lymph-node invasion patients, which underlie strong implication. Collectively, we propose novel significantly elevated resolved tool binary accurate detection other tumors female reproductive system.

Language: Английский

Citations

1
Multi-target therapeutic modulation with natural compounds towards DNA repair MRN-checkpoint sensor genes (MRN-CSGs) and oncogenic miRNAs in breast cancer patients: a Clinico-Informatic study DOI
Jitender Singh,

K.L. Khanduja,

Pramod Avti

et al.

Integrative Biology, Journal Year: 2024, Volume and Issue: 16

Published: Jan. 1, 2024

Abstract Breast cancer, more prevalent in women, often arises due to abnormalities the MRN-checkpoint sensor genes (MRN-CSG), responsible for DNA damage detection and repair. Abnormality this complex is suppression of various effectors such as siRNAs, miRNAs, transcriptional factors breast tumor progression. This study analyzed samples (n = 60) identified four common miRNAs (miR-1-3p, miR-210-3p, miR-16-5p, miR-34a-5p) out 12, exploring their interactions with MRN-CSG. The 3D structures these miRNA-MRN-CSG complexes displayed strong thermodynamic stability. Screening 7711 natural compounds resulted two (F0870–0001 F0922–0471) lowest ligand binding energies (ΔG −8.4 to−11.6 kcal/mol), targeting miRNAs. Docking results showed that one compound (PubChem id-5 281 614) bound all MRN-CSG components −6.2 −7.3 while F6782–0723 only RAD50 NBN. These exhibited minimal dissociation constants (Kd Ki) thermodynamically stable minimum free energy (MMGBSA) values. Molecular dynamics simulations indicated highly compound-MRN-CSG complexes, consistent RMSD, RMSF, residual correlation. top-selected robust intermolecular H-bonding, low carcinogenicity, toxicity, drug-like properties. Consequently, hold promise regulating miRNA repair mechanisms cancer therapy. Insight Box: investigated interact crucial highlighted −11.6 (miR-1-3p miR-34a-5p). Another 614, ΔG kcal/mol) components, targeted stability, favorable MMGBSA values, constants. confirmed stability properties compounds, indicating potential therapy by modulating mechanisms.

Language: Английский

Citations

0