Distinct Immune Landscape and Gene Expression Profiles in Breast Cancer: Young vs. Non-Young Patients DOI Creative Commons
Zijun Zhu, Chen Gao, Yongxin Li

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

Abstract Background Breast cancer remains a prevalent malignancy worldwide, particularly affecting younger women more aggressively. Significant differences in clinical and biological characteristics exist between breast with young patients (BCY) non-young (BCNY). However, the role of immune microenvironment these is not fully understood.Methods Data from Molecular Taxonomy Cancer International Consortium (METABRIC) database were analyzed to compare tumor-infiltrating cells (TIICs) gene expression BCY BCNY. The CIBERSORT algorithm was used estimate relative abundance 22 cell types, differentially expressed genes (DEGs) identified using "limma" package R.Results group had higher prevalence M0 macrophages activated dendritic cells, while BCNY exhibited greater infiltration CD4 memory T M2 macrophages, neutrophils. Differential analysis 11 significantly groups, such as FDCSP GABRP upregulated group. GSEA revealed that pro-inflammatory pathways, cytokine-cytokine receptor interaction, enriched group, pathways related metabolism extracellular matrix interactions Kaplan-Meier demonstrated high certain genes, NAT1, CA12, SRARP, associated better relapse-free survival.Conclusion exhibit distinct landscape characterized by levels contributing aggressive disease profile.

Language: Английский

ROS: A “booster” for chronic inflammation and tumor metastasis DOI

Anqi Chen,

Haifeng Huang,

S. S. Fang

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(6), P. 189175 - 189175

Published: Aug. 31, 2024

Language: Английский

Citations

25
Circular RNA circ_0004470 accelerates the occurrence of lung cancer by promoting DNA damage and cell cycle arrest DOI Creative Commons
Xueqi Li, Yufei Liu, Qiwen Zheng

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108456 - 108456

Published: March 1, 2025

Defects in the DNA damage response (DDR) are associated with tumorigenesis, and circular RNAs (circRNAs) can also affect occurrence progression of cancer by regulating gene expression. However, relationship between lung circRNAs remains unexplored. In this study, circ_0004470 was significantly upregulated various cells (H446, A549, H1299) as well carcinogenic animal models clinical samples. Circ_0004470 promoted cell cycle S phase arrest human pulmonary bronchial epithelial cells, inhibited repair, accelerated malignant transformation to continuous damage-inducing stimulation. repair binding specifically nucleotide excision complex XPC damage-specific protein 1 (DDB1), thus interacting process accelerating accumulation damage. These findings suggest that involved genetic damage-associated provide insight into mechanism which affects DDR during carcinogenesis.

Language: Английский

Citations

0
The protein deacetylase HDAC10 controls DNA replication in malignant lymphoid cells DOI Creative Commons
Andreas O Mieland, Giuseppe Petrosino, Mario Dejung

et al.

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

Published: April 29, 2025

Abstract Histone deacetylases (HDACs) comprise a family of 18 epigenetic modifiers. The biologically relevant functions HDAC10 in leukemia cells are enigmatic. We demonstrate that human cultured and primary acute B cell/T cell lymphoma require the catalytic activity for their survival. In such cells, controls MYC-dependent transcriptional induction DNA polymerase subunit POLD1. Consequently, pharmacological inhibition causes breaks an accumulation poly-ADP-ribose chains. These processes culminate caspase-dependent apoptosis. PZ48 does not damage resting proliferating normal blood cells. vivo against ALL is verified Danio rerio model. data reveal nuclear function HDAC10. MYC-POLD1 axis to maintain processivity replication genome integrity. This mechanistically defined “HDAC10ness” may be exploited as treatment option lymphoid malignancies.

Language: Английский

Citations

0
Combined SET7/9 and CDK4 inhibition act synergistically against osteosarcoma DOI
Y. Shi, Zhonghao Wang, Yiming Shao

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 708, P. 149808 - 149808

Published: March 20, 2024

Language: Английский

Citations

3
Antisense mediated blockade of Dickkopf 1 attenuates tumor survival, metastases and bone damage in experimental osteosarcoma DOI Creative Commons
Andrew Haskell, Simin Pan, Robert J. Reese

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 13, 2025

Osteosarcoma (OS) is the most common primary bone malignancy. The canonical Wnt inhibitor Dickkopf-1 (Dkk-1) has been implicated in destruction, tumor survival and metastases during OS. We examined role of Dkk-1 OS disease progression explored strategies for targeting its activity. enhances by amplifying a non-canonical pathway that upregulates aldehyde dehydrogenase 1A1. Targeting transcription with vivo morpholino (DkkMo) reduced enhanced osteogenic activity vitro. DkkMo as single agent slowed expansion, increased necrosis, inhibited preserved PDX model also frequency dividing cells reinitiated regenerative phenotype tumors stroma while reducing infiltration inflammatory cells. These findings indicate potential to safely target osteosarcoma growth, survival, destruction.

Language: Английский

Citations

0
AZD6738 Attenuates LPS-Induced Corneal Inflammation and Fibrosis by Modulating Macrophage Function and Polarization DOI Creative Commons

Longxiang Huang,

Yiran Luo

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

Published: Feb. 4, 2025

Language: Английский

Citations

0
Critical Signalling Pathways Activating Cellular Senescence and Immortalization DOI

D. S. Francis

Published: Jan. 1, 2025

Language: Английский

Citations

0
LINC01235 Promotes Clonal Evolution through DNA Replication Licensing‐Induced Chromosomal Instability in Breast Cancer DOI Creative Commons
Qi Zhang, Xuliren Wang,

Zhibo Shao

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Abstract Despite the development of HER2‐targeting drugs such as trastuzumab and T‐DXd, treatment resistance is a substantial challenge, often leading to relapse distant metastasis. Tumor heterogeneity in HER2‐positive breast cancer drives evolution resistant clones following therapeutic stress. However, targetable drivers anti‐HER2 are not thoroughly identified. This study aims use neoadjuvant‐targeted therapy cohorts patient‐derived organoid vitro model uncover potential resistance. it found that LINC01235 significantly enhances DNA replication licensing chromosomal instability, fostering clonal expansion evolution, ultimately increasing interventions. regulates global H3K27ac, H3K9ac, H3K36me3 modifications, promotes H2A.Z expression regulatory regions, increases accessibility factors their promoter regions. XRCC5 identified key component for maintaining genomic stability, crucial LINC01235's role licensing. Furthermore, strategies targeting LINC01235, including antisense oligonucleotides or ATR inhibitors, which showed promise overcoming explored. These findings underscore pivotal driving mechanisms highlight novel avenues targeted therapies improve outcomes patients with cancer.

Language: Английский

Citations

0
CDK8/19 inhibition attenuates G1 arrest induced by BCR-ABL antagonists and accelerates death of chronic myelogenous leukemia cells DOI Creative Commons
Alvina I. Khamidullina, Margarita A. Yastrebova, Alexandra V. Bruter

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 15, 2025

Imatinib mesylate (IM) and other BCR-ABL tyrosine kinase inhibitors (BCR-ABLi) are the mainstay of chronic myelogenous leukemia (CML) treatment. However, activation circumventing signaling pathways quiescence may limit BCR-ABLi efficacy. CDK8/19 Mediator kinases have been implicated in emergence non-genetic drug resistance. Dissecting effects pharmacological inhibition on CML survival response to BCR-ABLi, we found that a selective, non-toxic inhibitor (CDK8/19i) Senexin B (SenB) CDK8/19i sensitized K562 cells different via attenuation cell cycle arrest. In particular, SenB prevented IM-induced upregulation genes negatively regulate progression. also antagonized IM-activated p27Kip1 elevation thereby diminishing population G1-arrested cells. After transient G1 arrest, treated with IM + re-entered S phase, where they were halted underwent replicative stress. Consequently, combination intensified apoptotic death, measured by caspase 9 3, subsequent cleavage poly(ADPriboso)polymerase 1, positive Annexin V staining increase subG1 fraction. contrast, IM-treated BCR-ABL-positive KU812 cells, which did not induce p27Kip1, readily died regardless Thus, prevent quiescence-mediated escape from BCR-ABLi-induced apoptosis, suggesting strategy for avoiding relapse.

Language: Английский

Citations

0
FAM50A as a novel prognostic marker modulates the proliferation of colorectal cancer cells via CylinA2/CDK2 pathway DOI Creative Commons
Longhai Li,

Zhaoshuai Ji,

Guangyun Li

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(2), P. e0318776 - e0318776

Published: Feb. 25, 2025

Objective Colorectal cancer (CRC) is the third most prevalent malignant tumor type and second leading cause of cancer-related death. Sequence similarity family 50 member A (FAM50A) plays a vital role in numerous disease processes, including progression. This study aimed to evaluate prognostic significance FAM50A CRC explore its cell proliferation. Methods TCGA GTEX databases immunohistochemical staining (IHC) was used expression tissues. Patient survival data were assess using Kaplan–Meier analysis Cox regression analysis. The Cell Counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), colony-formation assays employed impact on Flow cytometry detect changes cycle. cycle cycle-related proteins measured via western blotting (WB) potential mechanisms involving progresses. Results results IHC revealed notable upregulation levels tissue compared with adjacent normal tissue. Moreover, positively correlated N TNM stages 145 patients CRC. construction nomogram that high indicator for poor overall Knockdown decreased proliferation ability, proportion EdU positive cells, number colonies, whereas overexpressing promoted proliferative phenotypes. Knocking down induced significant increase cells S phase. Meanwhile, CyclinA2 CDK2 significantly reduced after knocking down. Conclusion may be novel marker CRC, participate regulating progression by targeting CyclinA2/CDK2 signal pathway.

Language: Английский

Citations

0