RSK4 promotes the metastasis of clear cell renal cell carcinoma by activating RUNX1-mediated angiogenesis

Cancer Biology & Therapy, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 10, 2025

Ribosomal S6 protein kinase 4 (RSK4), a member of the serine‒threonine family, plays vital role in Ras‒MAPK pathway. This is responsible for managing several cellular activities, including cell growth, proliferation, survival, and mobility. In this study, we observed higher RSK4 expression clear renal carcinoma (ccRCC) than normal kidney tissue, overexpression might predict poor outcomes ccRCC patients. Notably, (RCC) rich blood vessels; therefore, study aimed to explore biological function progression its specific regulatory mechanism. We analyzed changes target genes through transcriptomic proteomic assessments. also conducted tube formation assays VEGF ELISAs understand angiogenesis. Additionally, evaluated effect RUNX1 on EPHA2 transcription using luciferase reporter gene assay that activating was negated after binding site mutated. Our findings suggested enhanced by stimulating secretion. Concurrently, vivo experiments confirmed expedited RCC metastasis evidence indicates may serve as new prognostic marker play metastasis.

Language: Английский

---

Integrating single-cell RNA-seq and bulk RNA-seq to explore prognostic value and immune landscapes of methionine metabolism-related signature in breast cancer

Frontiers in Genetics, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 14, 2025

Background Neoadjuvant, endocrine, and targeted therapies have significantly improved the prognosis of breast cancer (BC). However, due to high heterogeneity cancer, some patients cannot benefit from existing treatments. Increasing evidence suggests that amino acids their metabolites can alter tumor malignant behavior through reshaping microenvironment regulation immune cell function. Breast lines been identified as methionine-dependent, methionine restriction has proposed a potential treatment strategy. Methods We integrated transcriptomic single-cell RNA sequencing (ScRNA-seq) analyses based on The Cancer Genome Atlas (TCGA) database Gene Expression Omnibus (GEO) datasets. Then we applied weighted gene co-expression network analysis (WGCNA) Cox regression evaluate metabolism-related genes (MRGs) in BC, constructing validating prognostic model for BC patients. Immune landscapes immunotherapy were further explored. Finally, vitro experiments conducted assess expression function key APOC1. Results In this study, established validated signature eight methionine-related predict overall survival (OS) Patients stratified into high-risk low-risk groups according risk score. Further revealed significant differences between two terms pathway alterations, characteristics, checkpoint expression. Our study shed light relationship metabolism infiltration BC. APOC1, signature, was found be upregulated closely associated with infiltration. Notably, APOC1 primarily expressed macrophages. Subsequent demonstrated silencing reduced generation tumor-associated macrophages (TAMs) an M2 phenotype while decreasing proliferation, invasion, migration MDA-MB-231 MDA-MB-468 lines. Conclusion score consisting metabolism, which helps response regulating macrophage polarization

Language: Английский

---

Identifying Novel Aging-Related Biomarkers for Age-related Macular Degeneration with Integrative Bioinformatics Approaches

Theoretical and Natural Science, Journal Year: 2025, Volume and Issue: 90(1), P. 1 - 23

Published: Jan. 15, 2025

Age-related macular degeneration (AMD) is the leading cause of visual impairment in older adults worldwide and a condition that causes deprivation. There exist two subcategories this disease with wet form being focus our study. Using bioinformatic analysis, research conducted investigations to uncover genes related aging may be biomarkers for development AMD. First, we compared expression levels samples from AMD/CNV patients control group using GEO microarrays (GSE29801) order obtain differentially expressed (DEGs). WGCNA, combined functional enrichment utilized discover validate gene module crucial Differentially aging-related (DEARGs) were identified by overlapping significant sets. The subcellular location hub DEARGs their corresponding cell subpopulations determined predicted Geo dataset GSE155288. Pan-cancer analyses used confirm those function other diseases. Moreover, both Protein-Protein Interaction (PPI) AlphaFold prediction employed protein interaction among key DEARGs. Lastly, potential target drug was selected, portions them validated through drug-protein interactions. In further analysis result, collect set 7 divided into immune-related non-immune-related group. These groups uncovered distinct pathways AMD development, one triggering inflammatory responses promoting macrophage proliferation inducing choroidal neovascularization formation due malfunctioning growth regulator

Language: Английский

---

Inhibition of programmed cell death by melanoma cell subpopulations reveals mechanisms of melanoma metastasis and potential therapeutic targets

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 20, 2025

Melanoma is an aggressive type of skin cancer that arises from melanocytes, the cells responsible for producing pigment. In contrast to non-melanoma cancers like basal cell carcinoma and squamous carcinoma, melanoma more invasive. was distinguished by its rapid progression, high metastatic potential, significant resistance conventional therapies. Although it accounted a small proportion cases, accounts majority deaths caused due ability invade deep tissues, adapt diverse microenvironments, evade immune responses. These unique features highlighted challenges treating underscored importance advanced tools, such as single-cell sequencing, unravel biology develop personalized therapeutic strategies. Thus, we conducted analysis cellular composition within tumor tissues further subdivided into subpopulations. Through analyzing metabolic pathways, stemness genes, transcription factors (TFs) among in different phases (G1, G2/M, S) well between primary foci cells, investigated specific mechanisms underlying metastasis. We also revisited temporal trajectories subpopulations, identifying core subpopulation C0 SOD3 + cells. Our findings revealed close relationship pivotal oxidative pathways tissues. Additionally, analyzed prognostically relevant differentially expressed genes (DEGs) built predictive model associated with outcomes. selected gene IGF1 highest coefficient (coef) value analysis, experimentally validated essential function proliferation invasive metastasis melanoma. infiltration discovered critical roles played M1/M2 macrophages progression evasion. Furthermore, development malignant were closely various forms programmed death (PCD), including apoptosis, autophagic death, ferroptosis, pyroptosis. often resisted mechanisms, maintaining their growth inhibiting apoptosis evading death. Meanwhile, induction ferroptosis pyroptosis thought trigger responses helped suppress dissemination. A deeper understanding PCD provided foundation developing novel targeted therapies, potential enhance treatment efficacy. contributed prognostic models shed light on research directions concerning targets.

Language: Английский

---

APOC1 knockdown induces apoptosis and decreases angiogenesis in diffuse large B-cell lymphoma cells through blocking the PI3K/AKT/mTOR pathway

Biomolecules and Biomedicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous metastatic that can be treated by targeting angiogenesis. Apolipoprotein C1 (APOC1) plays significant role in the proliferation and metastasis of various malignant tumors; however, its DLBCL—particularly effects on angiogenesis—remains largely unexplored. This study investigates correlation between APOC1 expression patient prognosis DLBCL. Using gene knockdown, apoptosis, migration, invasion were assessed through flow cytometry, EDU assay, wound healing, Transwell assays. Additionally, human umbilical vein endothelial cells (HUVEC) angiogenesis was evaluated. Advanced techniques such as immunofluorescence, TUNEL immunohistochemical labeling employed to analyze knockdown PI3K/AKT/mTOR signaling pathway tumor formation nude mice. Results showed overexpressed DLBCL tissues cells, with high levels associated poor prognosis. In vitro experiments revealed increased apoptosis inhibited cell proliferation, invasion, HUVEC angiogenesis, protein cells. Similarly, vivo studies demonstrated significantly reduced growth, angiogenesis-related proteins, phosphorylated proteins promotes suppresses inhibiting pathway.

Language: Английский

---

The role of macrophages in liver metastasis: mechanisms and therapeutic prospects

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 17, 2025

Metastasis is a hallmark of advanced cancer, and the liver common site for secondary metastasis many tumor cells, including colorectal, pancreatic, gastric, prostate cancers. Macrophages in microenvironment (TME) promote cell through various mechanisms, angiogenesis immunosuppression, play unique role development metastasis. are affected by variety factors. Under conditions hypoxia increased acidity TME, more factors now found to polarization macrophages M2 type, exosomes amino acids. M2-type secretion such as VEGF, IL-1β, TGF-β1. subjected multiple regulatory mechanisms. They also interact with cells within co-regulate certain conditions, creation an immunosuppressive microenvironment. This interaction promotes metastasis, drug resistance, immune escape. Based on advent single-cell sequencing technology, further insights into macrophage subpopulations may help exploring new therapeutic targets future. In this paper, we will focus how affect well other each other, investigate mechanisms involved their potential targets.

Language: Английский

---

Bioinformatic methods uncover 5 diagnostic biomarkers associated with drug resistance and metastasis for gastrointestinal stromal tumor

Current Pharmaceutical Analysis, Journal Year: 2025, Volume and Issue: 21(2), P. 67 - 76

Published: Feb. 1, 2025

Language: Английский

---

Single-cell analysis reveals transcriptomic features and therapeutic targets in primary pulmonary lymphoepithelioma-like carcinoma

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 8, 2025

Abstract Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of non-small-cell lung cancer. Duo to the current lack precise targeted therapies, there an urgent need identify novel therapeutic targets. In this study, we perform single-nucleus transcriptome analysis on PPLELC samples reveal molecular tumor heterogeneity and characterize functional states immune cells within microenvironment. We critical malignant subpopulation characterized by elevated expression AKT3 FGFR2. Higher levels FGFR2 are associated with poorer patient outcomes. Moreover, treatment either inhibitor or significantly attenuates progression in patient-derived xenograft models. Our findings highlight as potential targets prognostic biomarkers, providing valuable insights for development rational therapies immunotherapeutic strategies.

Language: Английский

---

APOC1, transcriptionally regulated by FOXM1, promotes M2 macrophage polarization and cervical cancer progression

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Journal Year: 2025, Volume and Issue: 830, P. 111904 - 111904

Published: Jan. 1, 2025

Language: Английский

---

Apolipoprotein C1 and apoprotein E as potential therapeutic and prognostic targets for adrenocortical carcinoma

Cancer Biomarkers, Journal Year: 2025, Volume and Issue: 42(1)

Published: Jan. 1, 2025

Background Apolipoprotein C1 ( APOC1) and Apoprotein E (APOE) play important roles in lipid transport metabolism. In recent years, APOC1 APOE have been shown to key the occurrence development of various cancers. However, expression levels, gene regulatory networks, prognostic values, target predictions adrenocortical carcinoma (ACC) remain unclear. Methods Various bioinformatics analysis methods were used, including profiling interactive analysis, University Alabama at Birmingham cancer data portal, biomarker exploration solid tumors software, BioPortal for Cancer Genomics, search tool retrieval interacting genes/proteins, multiple association network integration algorithm, Metascape, transcriptional relationships unraveled by sentence-based text-mining, LinkedOmics, genomics drug sensitivity analysis. Results strongly downregulated patients with ACC. levels lower male ACC than those female patients. Furthermore, affected prognosis The main functions its altered neighboring genes (ANG) organophosphate ester transport, rRNA processing, positive regulation cytokine production. Cytolysis, protein ubiquitination, histone modification ANGs. transcription factor E2F1, tumor p53, miR-182, miR-493, Erb-B2 receptor tyrosine kinase 2, cyclin dependent 1 targets , positively associated immune cell infiltration . anti-programmed death immunotherapy Both pilaralisib elesclomol inhibited SW13 growth. Conclusions This study preliminarily clarified that might be potential therapeutic ACC, identified new treatment strategies

Language: Английский

---