Intracellular amphiregulin is critical for heterochromatin maintenance and genomic stability in response to replication stress inBRCA2mut/+mammary epithelial cells DOI

Tianqi Jiang,

Aiman A. Zein,

M.A. Christine Pratt

и другие.

Опубликована: Окт. 29, 2024

Abstract The BRCA2 tumor suppressor protein has roles in homologous recombination DNA repair and replication fork protection carriers of mutation the gene ( mut/+ ) are at high risk for breast cancers as a consequence genomic instability. Mammary epithelial cells (MECs) subjected to significant hormone-driven replication. MECs must therefore be able mitigate RS-induced chronic damage that could result cell death or senescence. In response acute RS hTERT-MECs, we have found EGFR ligand, amphiregulin (AREG) rapidly undergoes retrograde trafficking nucleus nuclear membrane (NM) association with lamin A resulting transient increase H3K9me3 heterochromatin most markedly hTERT-MECs. promoted NM incorporation prelamin was dependent on endogenous but not exogenous AREG. Prelamin is reported stabilize SUV39h1 expression C-terminal truncated AREG translocates increased SUV39h1, HP1α H3K9me3. knockdown reduced both accompanied by massive decompaction reduction global heterochromatin. Loss upon depletion damage, speed resulted firing new multiple origins. Knockdown also impacted activation type-1 interferon (IFN)-like promoting Chronic stimulated along FOXM1 ESR1 mRNA protein. Consistent this, AREG, ERα were detected hyperplastic regions human tissue. Overall, our work reveals critical unanticipated role maintenance induction preventing excessive senescence MECs. Since promotes expression, this may link aberrant expansion estrogen receptor-expressing mammary

Язык: Английский

Risk-benefits assessment of tamoxifen or raloxifene as chemoprevention for risk reduction of breast cancer among BRCA1 and BRCA2 carriers: a meta-analysis DOI Creative Commons
Ameen S. S. Alwashmi, Najeeb Ullah Khan, Tianhui Chen

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 25, 2025

Background: Breast cancer is a major global health burden, with hereditary factors such as BRCA1/2 mutations significantly increasing the lifetime risk. This meta-analysis aimed to evaluate outcomes of selective estrogen receptor modulators (SERMs), tamoxifen, and raloxifene chemopreventive agents for breast risk reduction in mutation carriers. Methods: A was conducted according PRISMA guidelines. PubMed, Cochrane Library, MEDLINE databases were searched relevant studies published between 2000 2024. Case-control observational cohort examining use tamoxifen/raloxifene carriers included. Data on incidence ratios also extracted. Quality assessed using Newcastle-Ottawa Scale (NOS). random-effects performed Review Manager (version 5.4.0). Results: Nine (13,676 women) Two had low risk, remaining seven moderate by NOS checklist. Pooled analysis showed decreased compared controls (RR 0.80, 95% CI 0.72–0.88, p = 0.04). The ratio among reduced after tamoxifen 1.82, 1.48–2.23, < 0.00001). Subgroup revealed SERM both BRCA1 1.51, 1.48–1.51) BRCA2 1.48, 1.40–1.58). heterogeneity ranged from 51 85%, representing high significance variation true effect sizes underlying different included studies. Whereas subgroups 98%, difference 0%, showing no response cancer. Conclusion: provides evidence that reduce women mutations. Chemoprevention efficacy similar Further research needed validate these findings optimize their high-risk populations.

Язык: Английский

Процитировано

0
Sequencing of high-frequency mutated genes in breast cancer (BRCA) and associated-functions analysis DOI
Xue‐Lian Li, Mei Yang, Liyuan Yang

и другие.

International Journal of Clinical and Experimental Pathology, Год журнала: 2025, Номер 18(2), С. 46 - 62

Опубликована: Янв. 1, 2025

Mutations or aberrant expression of genes in an organism tend not to be completely random and this cumulative effect predisposes the development malignant tumours. This study aims reveal possible high frequency mutated genes, then investigate their role development, prognosis, signalling pathway function drug resistance breast cancer. The cancer (BRCA) clinical samples were identified detected by high-throughput sequencing. High-frequency mutant counted. Gene profiles relationship with prognosis analysed throughout TCGA database. qRT-PCR was used analyse mRNA levels six high-frequency BRCA tissues cell lines. IHC protein tissues. linear interaction, single-cell layer clustering status influence immune infiltration degree among these bioinformatics analysis. STITCH cMAP datasets for gene interaction networks, association enrichment drug-transcriptome analyses. effects trastuzumab on proliferative capacity cells, as well determined CCK8 assay. that statistically found have mutations recruited present sequencing analysis included TP53, PIK3CA, NF1, TBX3, BRCA1 BRCA2. correlation further demonstrated using database: trend similar TCGA. showed BRCA2 higher tumor than normal samples, opposite a observed expressions displayed same IHC. Other results include 1) single resulted significant few overlapping regions; 2) different degrees infiltration; 3) between each other; 4) network had partially molecules; 5) PI3K key BRCA. Finally, proliferation ability confirmed optimal concentration its genes.

Язык: Английский

Процитировано

0
Multi-omics and drug development DOI

Saira Hamid,

Ajaz A. Bhat,

Muzafar Rasool Bhat

и другие.

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 147 - 171

Опубликована: Янв. 1, 2025

Процитировано

0
Role of PARP Inhibitors: A New Hope for Breast Cancer Therapy DOI Open Access

K De,

Malabendu Jana,

Bhabadeb Chowdhury

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2773 - 2773

Опубликована: Март 19, 2025

Tumors formed by the unchecked growth of breast cells are known as cancer. The second most frequent cancer in world is It common among females. In 2022, 2,296,840 women were diagnosed with therapy evolving through development Poly (ADP-ribose) polymerase (PARP) inhibitors, which offering people specific genetic profiles new hope research into disease continues. focuses on patients BRCA1 and BRCA2 mutations. This review summarizes recent mechanisms action PARP inhibitors their implications for therapy. We how therapeutic applications developing highlight studies showing effectiveness these medicines whether used alone or combination. Furthermore, significance customized highlighted enhancing patient outcomes we address function testing identifying candidates inhibition. Recommendations future areas to maximize potential also included, along challenges limits clinical usage. objective this improve our comprehension complex interaction between biology knowledge will help guide screening approaches, practice, support preventive initiatives at risk.

Язык: Английский

Процитировано

0
The Function of Circular RNAs in Regulating Wnt/β-Catenin Signaling: An Innovative Therapeutic Strategy for breast and gynecological Cancers DOI

Samaneh Kahkesh,

Neda Hedayati,

Payman Rahimzadeh

и другие.

Pathology - Research and Practice, Год журнала: 2025, Номер unknown, С. 155944 - 155944

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Current landscape of cancer genomics research in sub-Saharan Africa – a review of literature DOI Creative Commons
Lemchukwu Amaeshi, Kehinde S. Okunade, Rose Anorlu

и другие.

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Апрель 17, 2025

Cancer poses a significant public health challenge in sub-Saharan Africa, region that has traditionally struggled with infectious diseases. Although communicable diseases remain the leading cause of mortality Africa (SSA), there been rise morbidity and rates associated non-communicable (NCDs), recent years. As 2019, NCDs accounted for 37% deaths, representing an increase from 24% recorded 2000. is fundamentally genetic disorder, genomic research provided deeper understanding its biology to identification biomarkers early cancer detection advancement precision oncology. However, despite Africa’s rich diversity burden, continent remains underrepresented global research. This underrepresentation mainly due challenges such as insufficient funding, inadequate infrastructure, limited pool trained professionals. these obstacles, initiatives like H3Africa Consortium, African BioGenome Project, Prostate Transatlantic Consortium (CaPTC), amongst others, have made strides funding developing local capacity infrastructure In this review, we discuss unique characteristics common cancers highlight faced implementation research, explore potential solutions current instituted foster region.

Язык: Английский

Процитировано

0
A comprehensive review of traditional medicinal plants and their role in ovarian cancer treatment DOI

Banuppriya Palani,

Renu Vajjiravelu,

Rajeshkumar Shanmugam

и другие.

South African Journal of Botany, Год журнала: 2025, Номер 181, С. 426 - 445

Опубликована: Апрель 28, 2025

Язык: Английский

Процитировано

0
Germline pathogenic variants among high hereditary risk patients with breast and ovarian cancer and unaffected subjects in Lebanese Arab women DOI
Hiba Moukadem,

Mohamad Fakhreddine,

Nada Assaf

и другие.

World Journal of Clinical Oncology, Год журнала: 2024, Номер 15(12), С. 1481 - 1490

Опубликована: Окт. 22, 2024

BACKGROUND The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need low middle-income countries. AIM To determine the with individuals. METHODS We retrospectively reviewed records variant due to between 2010-2020. Data was collected analyzed on Excel sheet. RESULTS In total, 358 individuals were included, including 257 101 relatives or cancer. susceptibility gene (BRCA) 1/2 8.63% (19/220) cancer, 15.1% (5/33) those Among 25 220 tested by next-generation sequencing, 3 had other than BRCA1/2 . highest observed aged 40 years a positive family history, where 20.1% (9/43). subjects, 31.1% (14/45) same their corresponding relatives. because history without known factors, 5.35% (3/56) BRCA1 BRCA2 c.131G>T nucleotide change noted one patient two unrelated variant. CONCLUSION This study showed variants, 31% variant, while 5.3% who BRCA

Язык: Английский

Процитировано

0
Intracellular amphiregulin is critical for heterochromatin maintenance and genomic stability in response to replication stress inBRCA2mut/+mammary epithelial cells DOI

Tianqi Jiang,

Aiman A. Zein,

M.A. Christine Pratt

и другие.

Опубликована: Окт. 29, 2024

Abstract The BRCA2 tumor suppressor protein has roles in homologous recombination DNA repair and replication fork protection carriers of mutation the gene ( mut/+ ) are at high risk for breast cancers as a consequence genomic instability. Mammary epithelial cells (MECs) subjected to significant hormone-driven replication. MECs must therefore be able mitigate RS-induced chronic damage that could result cell death or senescence. In response acute RS hTERT-MECs, we have found EGFR ligand, amphiregulin (AREG) rapidly undergoes retrograde trafficking nucleus nuclear membrane (NM) association with lamin A resulting transient increase H3K9me3 heterochromatin most markedly hTERT-MECs. promoted NM incorporation prelamin was dependent on endogenous but not exogenous AREG. Prelamin is reported stabilize SUV39h1 expression C-terminal truncated AREG translocates increased SUV39h1, HP1α H3K9me3. knockdown reduced both accompanied by massive decompaction reduction global heterochromatin. Loss upon depletion damage, speed resulted firing new multiple origins. Knockdown also impacted activation type-1 interferon (IFN)-like promoting Chronic stimulated along FOXM1 ESR1 mRNA protein. Consistent this, AREG, ERα were detected hyperplastic regions human tissue. Overall, our work reveals critical unanticipated role maintenance induction preventing excessive senescence MECs. Since promotes expression, this may link aberrant expansion estrogen receptor-expressing mammary

Язык: Английский

Процитировано

0