MiR-26a-1 Promotes DNA Damage Repair by Inhibiting Sirt1 and KDM5A in Human Liver Cancer Stem Cells DOI Creative Commons
Liyan Wang, Xiaonan Li,

Rushi Qin

et al.

Research Square (Research Square), Journal Year: 2021, Volume and Issue: unknown

Published: March 1, 2021

Abstract Background: Although miR-26a-1 was down-regulated expressin in several cancers, the role of miR-26a-1in malignancies has yet to be systematically elucidated. Methods: RT-PCR, Western blotting and tumorigenesis test vitro vivo were performed analyze signaling pathway. Results: inhibits NAD(+)-dependent deacetylase Sirt1 expression by targeting 3' non-coding region which enhances acetylation modification H4 on 16th lysine histone protein arginine methyltransferase PRMT6. Therefore, promotes methylation POLB (R137) histone. On other hand, KDM5A its region, H3 ysine 4. Moreover, SETD2 dependent H3K4me3 further increases trimethylation 36 . Significantly, formation DNA damage repair complex (Rad51-PARP1-ATR-ATM-hMSH6-XRCC-POLB-SKP2) via H3K36me3. In particular, it found that inhibited function long RNA HULC promoted complex. Furthermore, ability promoting bind site, thereby inhibiting liver cancer stem cells. enhanced binding H3F3A Skp2, CUL1, F-box at site ubiquitination H3F3A, Histone replaces degrading realizing renewal histones after repair. It instability microsatellites repair, affecting cyclins kinases cells, such as, CDK2 CyclinE , CDK4, CyclinD1, CDK6, CDK8, CyclinM2, CDK15, pRB, PCNA, MAP3K2, PGK1 RB, P18, P21/WAF1/Cip1, thus growth cells Strikingly, rescued-test confirmed excessive abrogated oncogenic miR-26a-1. Conclusions: miR26a-1 may acts as potential biomarker therapeutic target for cancer.

Language: Английский

Poly(ADP-Ribose) Polymerase (PARP) Inhibitors for Cancer Therapy: Advances, Challenges, and Future Directions DOI Creative Commons
Denys Bondar, Yevgen Karpichev

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1269 - 1269

Published: Oct. 9, 2024

Poly(ADP-ribose) polymerases (PARPs) are crucial nuclear proteins that play important roles in various cellular processes, including DNA repair, gene transcription, and cell death. Among the 17 identified PARP family members, PARP1 is most abundant enzyme, with approximately 1-2 million molecules per cell, acting primarily as a damage sensor. It has become promising biological target for anticancer drug studies. Enhanced expression present several types of tumors, such melanomas, lung cancers, breast correlating low survival outcomes resistance to treatment. inhibitors, especially newly developed third-generation inhibitors currently undergoing Phase II clinical trials, have shown efficacy agents both single drugs sensitizers chemo- radiotherapy. This review explores properties, characteristics, challenges discussing their development from first-generation compounds, more sustainable synthesis methods discovery new anti-cancer agents, mechanisms therapeutic action, potential targeting additional targets beyond catalytic active site proteins. Perspectives on green chemistry also discussed.

Language: Английский

Citations

9
Targeting of the 8-oxodG Base Excision Repair Pathway for Cancer Therapy DOI Creative Commons

Anna Piscone,

Francesca Gorini, Susanna Ambrosio

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 112 - 112

Published: Jan. 14, 2025

Genomic integrity is critical for cellular homeostasis, preventing the accumulation of mutations that can drive diseases such as cancer. Among mechanisms safeguarding genomic stability, Base Excision Repair (BER) pathway plays a pivotal role in counteracting oxidative DNA damage caused by reactive oxygen species. Central to this are enzymes like 8-oxoguanine glycosylase 1 (OGG1), which recognize and excise 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) lesions, thereby initiating series repair processes restore integrity. BER inhibitors have recently been identified promising approach cancer therapy, increasing sensitivity cells radiotherapy chemotherapy. By exploiting tumor-specific dependencies synthetic lethal interactions, these could be used selectively target while sparing normal cells. This review provides robust reference scientific researchers, offering an updated perspective on small-molecule targeting 8-oxodG-BER highlighting their potential expanding treatment strategies.

Language: Английский

Citations

0
Defective DNA Repair: A Putative Nexus Linking Immunological Diseases, Neurodegenerative Disorders, and Cancer DOI
Safaa Othman Andarawi, Ľudmila Vodičková, Anusha Uttarilli

et al.

Mutagenesis, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

DNA damage is a common event in cells, resulting from both internal and external factors. The maintenance of genomic integrity vital for cellular function physiological processes. inadequate repair results the instability, which has been associated with development progression various human diseases. Accumulation can lead to multiple diseases, such as neurodegenerative disorders, cancers, immune deficiencies, infertility aging. This comprehensive review delves impact alterations response genes (DDR) tries elucidate how what extent same traits modulate diverse major cancer, immunological disorders. DDR apparently trait connecting important complex disorders humans. However, pathogenesis above diseases are different leading divergent consequences. It discover switch(es) that direct further pathogenic process either proliferative, or degenerative Our understanding influence on may enable strategies prevent, diagnose, treat these In our article, we analysed publicly available GWAS summary statistics NHGRI-EBI Catalog identified 12,009 single nucleotide polymorphisms (SNPs) cancer. Among these, 119 SNPs were found pathways, exhibiting significant p-values. Additionally, 44 linked cancer types (NDDs), including four located DDR-related genes: ATM, CUX2, WNT3. Furthermore, 402 two gene RAD51B. highlights versatility pathway multifactorial specific mechanisms regulate initiate distinct processes remain be elucidated.

Language: Английский

Citations

0
Anemarchalconyn, a natural alkyne ketone compound, inhibits HCC cell growth by suppressing Polθ and inducing synthetic lethality in Homologous recombination deficiency cells DOI
Junnan Li,

Wenwen Deng,

Tong Zhou

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156679 - 156679

Published: March 1, 2025

Language: Английский

Citations

0
Hypoxia-Induced DNA Damage Response and Genomic Instability Dictate Cancer Treatment Response DOI

Suniti Ahuja,

Preeti Gupta,

Gnana Ajay

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Role of MRE11 in DNA damage repair pathway dynamics and its diagnostic and prognostic significance in hereditary breast and ovarian cancer DOI Creative Commons
Bhoomi Tarapara, Franky D. Shah

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 9, 2025

DNA damage repair pathway genes are key components for maintaining genomic stability and mainly associated with hereditary breast ovarian cancer. The present study aimed to investigate the gene expression profile of genes, including BRCA1, BRCA2, ATM, TP53, CHEK2, MRE11, RAD50, BARD1, PALB2, NBN, in cancer patients using quantitative real-time PCR. showed significant upregulation most HBOC compared controls, except which was downregulated. Receiver operating characteristic (ROC) curve analysis revealed that MRE11 (p < 0.001), BRCA1 BRCA2 PALB2 0.001) can be used as potential diagnostic biomarkers Spearman correlation RAD50 significantly BRCA1/2 mutation status = 0.05). Furthermore, bivariate a strong positive between BARD1 NBN genes. Kaplan-Meier survival reduces better overall survival. findings may lead understanding molecular mechanisms underlying cancer, suggesting its role prognostic marker.

Language: Английский

Citations

0
Design, synthesis and biological evaluation of multitarget hybrid molecules containing NHC-Au(I) complexes and carbazole moieties DOI
Alfonsina D’Amato, Domenico Iacopetta, Jessica Ceramella

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 277, P. 116757 - 116757

Published: Aug. 9, 2024

Language: Английский

Citations

3
Cell-free Xenopus egg extracts for studying DNA damage response pathways DOI Open Access

Steven Cupello,

Christine Richardson, Shan Yan

et al.

The International Journal of Developmental Biology, Journal Year: 2016, Volume and Issue: 60(7-8-9), P. 229 - 236

Published: Jan. 1, 2016

In response to a variety of DNA replication stress or damaging agents, the damage (DDR) pathways are triggered for cells coordinate repair, cell cycle checkpoints, apoptosis, and senescence. Cell-free Xenopus egg extracts, derived from eggs African clawed frogs (Xenopus laevis), have been widely used studies concerning DDR pathways. this review, we focus on how different experimental systems established using extracts investigate that activated in stress, double-strand breaks (DSBs), inter-strand crosslinks (ICLs), oxidative stress. We summarize molecular details dissected by mechanistic with extracts. also provide an update regulation translesion synthesis (TLS) polymerases (Pol ĸ REV1) A better understanding Xenopus egg has opened new avenues future cancer therapeutics. Finally, offer our perspectives directions

Language: Английский

Citations

23
Design, Synthesis and Biological Evaluation of Multitarget Hybrid Molecules Containing Nhc-Au(I) Complexes and Carbazole Moieties DOI
Annaluisa Mariconda, Assunta D’Amato, Domenico Iacopetta

et al.

Published: Jan. 1, 2024

N-heterocyclic carbenes (NHCs) represent suitable ligands for rapid and efficient drug design, because they offer the advantage of being easily chemically modified can bind several substituents, including transition metals as, instance, gold derivatives. Gold-NHC complexes possess various biological activities were demonstrated good candidates as anticancer drugs. Besides, carbazole derivatives are characterized by pharmacological properties, such anticancer, antibacterial, anti-inflammatory, anti-psychotropic. Amongst latter, N-thioalkyl carbazoles proved to inhibit cancer cells damaging nuclear DNA, through inhibition human topoisomerases. Herein, we report synthesis, evaluation nine new hybrid molecules in which NHC-Au(I) N-alkylthiolated linked together, order obtain novel multitarget agents. We that lead antioxidant with high potential useful tools treating distinct aspects diseases, amongst them cancer.

Language: Английский

Citations

1
Mixtures of Three Mortaparibs with Enhanced Anticancer, Anti-Migration, and Antistress Activities: Molecular Characterization in p53-Null Cancer Cells DOI Open Access
Renu Wadhwa, Shiming Yang, Hazna Noor Meidinna

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(12), P. 2239 - 2239

Published: June 17, 2024

Mortalin, a member of the Hsp70 family proteins, is commonly enriched in many types cancers. It promotes carcinogenesis and metastasis multiple ways which inactivation tumor suppressor activity p53 has been firmly established. The downregulation mortalin and/or disruption mortalin–p53 interactions by small molecules earlier shown to activate function yielding growth arrest/apoptosis cancer cells. Mortaparibs (Mortaparib, MortaparibPlus, MortaparibMild) are chemical inhibitors isolated cell-based two-way screening involving (i) shift staining pattern from perinuclear (characteristics cells) pancytoplasmic normal (ii) nuclear enrichment p53. They have similar structures also cause inhibition PARP1 hence were named Mortaparibs. In present study, we report anticancer anti-metastasis MortaparibMild (4-[(4-amino-5-thiophen-2-yl-1,2,4-triazol-3-yl)sulfanylmethyl]-N-(4-methoxyphenyl)-1,3-thiazol-2-amine) p53-null By extensive molecular analyses cell proliferation, arrest, apoptosis pathways, demonstrate that although it causes relatively weaker cytotoxicity compared Mortaparib its lower concentrations equally potent inhibit migration. We developed combinations (called MortaparibMix-AP, MortaparibMix-AM, MortaparibMix-AS) consisting different ratios three for specifically enhancing their anti-proliferation, anti-migration, antistress activities, respectively. Based on control treated cells, suggest mixtures may be considered further laboratory clinical studies validating use treatment as well prevention relapse metastasis.

Language: Английский

Citations

1