Tumor-derived exosomal KPNA2 activates fibroblasts and interacts with KIFC1 to promote bladder cancer progression, a process inhibited by miR-26b-5p

Cellular & Molecular Biology Letters, Journal Year: 2025, Volume and Issue: 30(1)

Published: Feb. 16, 2025

Abstract Background Recent studies have illuminated the complexities of treating advanced bladder cancer (BCa), underscoring importance comprehending its molecular mechanisms for creating novel therapies. While role Karyopherin a2 ( KPNA2 ) in promoting BCa growth is established, precise mechanism remains elusive. Methods To investigate regulatory BCa, we employed a comprehensive approach integrating clinical case data and bioinformatics analysis to evaluate expression tissues. Mechanisms by were examined using both vivo vitro models. Results Our research reveals that miR-26b-5p acts as an anticancer factor targeting inhibiting expression. Furthermore, observed interaction between Kinesin Family Member C1 KIFC1 facilitates transition cells into G2/M phase, thereby tumor advancement via activation Phosphoinositide 3-kinase (PI3K)- Protein Kinase B (AKT) pathway. Importantly, this investigation first identify exosomes originating from Plasma patients with exhibited notably increased levels compared healthy controls, suggesting potential new indicator. Additionally, triggered conversion fibroblasts cancer-associated (CAFs), which secreted elevated interleukin-6 (IL-6), contributing tumor-supporting environment. Conclusions These findings suggest key gene promotes progression, can potentially be marker, may serve therapeutic target BCa. Graphical

Language: Английский

---

Unveiling the impact of CDK8 on tumor progression: mechanisms and therapeutic strategies

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: March 28, 2024

CDK8 is an important member of the cyclin-dependent kinase family associated with transcription and acts as a key “molecular switch” in Mediator complex. regulates gene expression by phosphorylating factors can control process through Previous studies confirmed that oncogenic factor, making it potential tumor biomarker promising target for therapy. However, has also been to be suppressor, indicating not only promotes development tumors but may involved suppression. Therefore, dual role worth further exploration summary. This comprehensive review delves into intricate involvement transcription-related processes, well its signaling pathways related tumorigenesis, focus on critical part driving cancer progression.

Language: Английский

---

A Cross-Sectional Pilot Analysis of Downregulated Circulating MicroRNAs in Laryngeal Cancer

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 830 - 830

Published: March 31, 2025

Background and Objectives: Despite notable advances in diagnosing managing laryngeal cancer, the disease continues to present challenges, particularly advanced stages. Circulating microRNAs (miRNAs) are increasingly recognized as accessible biomarkers for cancer detection follow-up. This exploratory study centers on identifying evaluating miRNAs that specifically downregulated carcinoma patients, aiming clarify their clinical relevance distinguishing pre- post-therapeutic states. Methods: A total of 30 patients with provided paired blood samples before after undergoing surgical or non-surgical treatment. To reduce variability resource demand, each set 10 was pooled into three pre-treatment groups (P1, P2, P3) corresponding post-treatment (C1, C2, C3). Total RNA, including miRNAs, isolated from both plasma exosomes, followed by qPCR-based profiling (Qiagen platform). Downregulated were singled out through statistical comparisons using Mann–Whitney U tests; receiver operating characteristic (ROC) analyses logistic regression further applied assess diagnostic utility. Results: Seven demonstrated significant downregulation (fold changes ranging 0.20 0.64, p < 0.05). Notably, hsa-miR-107 hsa-let-7a-5p showed marked reductions approximately fivefold (p 0.01), suggesting a strong association active tumor presence. In ROC analysis, achieved an area under curve (AUC) 0.78 (95% CI: 0.62–0.90) 72% sensitivity 74% specificity differentiating model incorporating candidates produced odds ratios between 0.52 0.64 0.05), pointing potential additive value decision-making. Conclusions: These preliminary findings indicate certain when suppressed circulation, may be linked oncogenic milieu cancer. Confirming these observations larger, multicenter investigations is critical, but this pilot work underscores promise activity guides therapy response.

Language: Английский

---

MAT2A inhibits the ferroptosis in osteosarcoma progression regulated by miR-26b-5p

Journal of bone oncology, Journal Year: 2023, Volume and Issue: 41, P. 100490 - 100490

Published: June 25, 2023

Osteosarcoma (OS) is the most frequent primary malignant bone tumor. Ferroptosis, a form of regulated cell death, key tumor suppression mechanism. Although methionine adenosyltransferase II alpha (MAT2A) has been reported to inhibit several cells, it unclear whether inhibition MAT2A in OS cells can reduce ferroptosis. CCK-8, flow cytometry, and Transwell assays were performed evaluate viability, apoptosis/cycle, migration, respectively. The levels ferrous iron glutathione (GSH) measured degree Western blot analysis was detect protein MAT2A, p-STAT3 (Ser727)/STAT3, solute carrier family 7 member 11 (SLC7A11) cells. significantly upregulated specimens high expression associated with poorer prognosis patients. shRNA targeting increased apoptosis, triggered cycle arrest G2 phase, attenuated migration ability vitro. depletion dramatically inhibited progression vivo. Overexpression rescued caused by miR-26b-5p. knockdown promoted miR-26b-5p/MAT2A regulates ferroptosis controlling SLC7A11 expressions. Taken together, our study displayed that triggers increasing intracellular inhibiting STAT3/SLC7A11 axis. Our results reveal MAT2A-mediated defense mechanism used propose potential ferroptosis-inducing strategy for treatment

Language: Английский

---

Elucidating shared biomarkers in gastroesophageal reflux disease and idiopathic pulmonary fibrosis: insights into novel therapeutic targets and the role of angelicae sinensis radix

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 13, 2024

Background: The etiological underpinnings of gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF) remain elusive, coupled with a scarcity effective therapeutic interventions for IPF. Angelicae sinensis radix (ASR, also named Danggui) is Chinese herb potential anti-fibrotic properties, that holds promise as agent Objective: This study seeks to elucidate the causal interplay mechanisms underlying coexistence GERD Furthermore, it aims investigate regulatory effect ASR on this complex relationship. Methods: A two-sample Mendelian randomization (TSMR) approach was employed delineate connection between IPF, Phennoscanner V2 mitigate confounding factors. Utilizing single nucleotide polymorphism (SNPs) publicly available microarray data, we analyzed targets related IPF in GERD. Network pharmacology molecular docking were explore efficacy treating GERD-related External datasets subsequently utilized identify diagnostic biomarkers Results: IVW analysis demonstrated positive relationship (IVW: OR = 1.002, 95%CI: 1.001, 1.003; p &lt; 0.001). Twenty-five shared differentially expressed genes (DEGs) identified. GO functional revealed enrichment neural, cellular, brain development processes, concentrated chromosomes plasma membranes, protein binding activation involvement. KEGG unveiled proteoglycan, ERBB, neuroactive ligand-receptor interaction pathways cancer. Protein-protein (PPI) identified seven hub genes. 104 components targeted five (PDE4B, DRD2, ERBB4, ESR1, GRM8), confirming their excellent efficiency. GRM8 ESR1 emerged (ESR1: AUC 0.762, 0.725; GRM8: 0.717, 0.908). validated external datasets. Conclusion: establishes link identifying key two exhibits intervention favorable characteristics, positioning promising candidate may involve cell responses fibroblast growth factor stimulation steroidal hormone-mediated signaling pathways.

Language: Английский

---

Bioinformatics analysis and experimental verification of the cancer-promoting effect of DHODH in clear cell renal cell carcinoma

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: May 25, 2024

Clear cell renal carcinoma (ccRCC) is a malignant tumor of the urinary system. To explore potential mechanisms DHODH in ccRCC, we analyzed its molecular characteristics using public databases. TCGA pan-cancer dataset was used to analyze expression different cancer types and ccRCC assess differential expression, prognosis correlation, immune infiltration, single-gene, functional enrichment due DHODH. The GSCALite CellMiner databases were employed drugs perform docking analysis with Protein-protein interaction networks ceRNA regulatory constructed multiple effect on confirmed vitro. highly expressed ccRCC. Immune infiltration revealed that may be involved regulating immunosuppressive cells such as Tregs. Notably, influenced progression by forming molecules, hsa-miR-26b-5p UMPS significantly enhanced cells. Several drugs, lapatinib, silmitasertib, itraconazole, dasatinib, sensitive exhibited strong binding it. Thus, promote candidate effective therapeutic target for

Language: Английский

---

Induction, Growth, Drug Resistance, and Metastasis: A Comprehensive Summary of the Relationship between STAT3 and Gastric Cancer

Heliyon, Journal Year: 2024, Volume and Issue: unknown, P. e37263 - e37263

Published: Sept. 1, 2024

Language: Английский

---

Construction of a Cancer Stem Cell Marker Genes-Related 22-Gene Signature for Overall Survival Prediction in High-Risk Wilms’ Tumor

Fetal and Pediatric Pathology, Journal Year: 2024, Volume and Issue: 43(5), P. 351 - 365

Published: Aug. 6, 2024

This study aimed to investigate the comprehensive expression profile of cancer stem cell (CSC)-related genes and construct a prognostic signature for overall survival (OS) prediction in high-risk Wilms' tumor (WT).

Language: Английский

---

Comprehensive Bioinformatics Analysis Reveals the Potential Role of the hsa_circ_0001081/miR-26b-5p Axis in Regulating COL15A1 and TRIB3 within Hypoxia-Induced miRNA/mRNA Networks in Glioblastoma Cells

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2236 - 2236

Published: Oct. 1, 2024

The intrinsic molecular heterogeneity of glioblastoma (GBM) is one the main reasons for its resistance to conventional treatment. Mesenchymal GBM niches are associated with hypoxic signatures and a negative influence on patients' prognosis. To date, competing endogenous RNA (ceRNA) networks have been shown broad impact progression various cancers. In this study, we decided construct hypoxia-specific microRNA/ messengerRNA (miRNA/mRNA) putative circular (circRNA) regulatory component using available bioinformatics tools.

Language: Английский

---

SNHG6 facilitates the epithelial-mesenchymal transition and metastatic potential of esophageal squamous carcinoma through miR-26b-5p/ ITGB1 axis

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Oct. 23, 2024

Long non-coding RNAs (lncRNAs), such as SNHG6, have been identified crucial regulators in the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). Although role SNHG6 ESCC is not completely understood, our findings demonstrated that expression upregulated tissues compared to adjacent normal tissues. Furthermore, elevated levels are significantly correlated with higher TNM stage and poorer clinical prognosis patients. Functionally, both vivo vitro experiments shown knocking down inhibits proliferation, invasion, metastasis. Luciferase reporter assays Ago2-RIP assay confirm functions a competing endogenous RNA (ceRNA) by sponging miR-26b-5p modulate ITGB1 ESCC. Given instrumental EMT metastasis, we assessed EMT-related proteins. The suggest reduced can reverse induced lncRNA SHNG6, through rescue analysis. Overall, this study aims elucidate molecular mechanisms which promotes metastasis ESCC, providing novel theoretical foundation for understanding identifying new targets improving outcomes metastatic

Language: Английский

---