17β-Estradiol Through Activating G Protein-Coupled Estrogen Receptor Exacerbated the Complication of Benign Prostate Hyperplasia in Type 2 Diabetes Mellitus by Inducing Prostatic Proliferation DOI
Tingting Yang,

Zhen Qiu,

YuTian He

et al.

Published: Jan. 1, 2023

Background: Benign prostate hyperplasia (BPH) was one of the major chronic complications type 2 diabetes mellitus (T2DM), and sex steroid hormones were common risk factors for occurrence T2DM BPH.Methods: The profiles simultaneous quantified by LC-MS/MS in clinical serum patients, including simple BPH, new diagnosed T2DM, complicated with BPH matched healthy subjects. Clinical tissues, G protein-coupled estrogen receptor (GPER) inhibitor G15, GPER knockdown lentivirus, YAP1 Verteporfin, knockdown/overexpression targeted metabolomics analysis, Co-IP assays used to investigate molecular mechanisms dysregulated pathological process BPH.Findings: Along prostatic epithelial cells (PECs) proliferation, patients. Sex hormone metabolic patients had greatest degree separation from that As contributor hormones, elevated 17β-estradiol (E2) a significant positive relationship characteristics BPH. E2 through activating exacerbated high glucose (HG)-induced PECs proliferation formation YAP1-TEAD4 heterodimer via Hippo signaling. Knockdown or inhibition GPER-mediated Hippo-YAP1 signaling suppressed HG co-cultured BPH-1 cells. anti-proliferative effects verteporfin, an YAP1, blocked overexpression cells.Interpretation: Inactivating E2/GPER/Hippo/YAP1 might be effective delaying progression inhibiting proliferation.Clinical Trial Registration Details: This study registered Chinese Register (No. ChiCTR1800020339).Funding Information: work supported National Natural Science Foundation China (81973377, 81903689, 82073906 82273987), Key Jiangsu Higher Education Institutions (19KJA460008 19KJB350006), Priority Academic Program Development (PAPD), initializing Fund Xuzhou Medical University (D2018011), Postgraduate Research Practice Innovation Province (KYCX22-2966 KYCX23-2967). Declaration Interests: authors declare no competing interests. Ethics Approval Statement: All procedures studies performed according Helsinki. approved Committee Affiliated Hospital XYFY2018-KL093).

Language: Английский

Autophagy flux in bladder cancer: Cell death crosstalk, drug and nanotherapeutics DOI
Kuan Liu, Huijing Chen, Yanhong Li

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 591, P. 216867 - 216867

Published: April 7, 2024

Language: Английский

Citations

5
Senescence-specific molecular subtypes stratify the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer DOI Creative Commons

Luzhe Yan,

Haisu Liang,

Tiezheng Qi

et al.

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

Published: Feb. 19, 2025

Bladder cancer (BLCA) is notably associated with advanced age, characterized by its high incidence and mortality among the elderly. Despite promising advancements in models that amalgamate molecular subtypes treatment prognostic outcomes, considerable heterogeneity BLCA poses challenges to their universal applicability. Consequently, there an urgent need develop a new subtyping system focusing on critical clinical feature of BLCA: senescence. Utilizing unsupervised clustering Cancer Genome Atlas Program (TCGA)-BLCA cohort, we crafted senescence-associated classification precision quantification (Senescore). This method underwent systematic validation against established subtypes, strategies, immune tumor microenvironment (TME), relevance checkpoints, identification potential therapeutic targets. External validations were conducted using Xiangya IMvigor210 meta-cohort, multiplex immunofluorescence confirming correlation between Senescore, infiltration, cellular Notably, patients categorized within higher Senescore group predisposed basal subtype, showcased augmented harbored elevated driver gene mutations, exhibited increased secretory phenotype (SASP) factors expression transcriptome. poorer prognoses, these revealed greater responsiveness immunotherapy neoadjuvant chemotherapy. Our informed age-related features, accurately depict age-associated biological traits application BLCA. Moreover, this personalized assessment framework poised identify senolysis targets unique BLCA, furthering integration aging research into strategies.

Language: Английский

Citations

0
Hyperoxia exposure induces ferroptosis and apoptosis by downregulating PLAGL2 and repressing HIF-1α/VEGF signaling pathway in newborn alveolar typeII epithelial cell DOI Creative Commons
Yuting Zhu,

Hongmei Hou,

Yawen Li

et al.

Redox Report, Journal Year: 2024, Volume and Issue: 29(1)

Published: Aug. 5, 2024

Backgroud Bronchopulmonary dysplasia (BPD) is one of the most important complications plaguing neonates and can lead to a variety sequelae. ability HIF-1α/VEGF signaling pathway promote angiogenesis has an role in neonatal lung development.

Language: Английский

Citations

4
Regulation of trophectoderm morphogenesis by small GTPase RHOA through HIPPO signaling-dependent and -independent mechanisms in mouse preimplantation development DOI
Yusuke Marikawa, Vernadeth B. Alarcón

Differentiation, Journal Year: 2025, Volume and Issue: 141, P. 100835 - 100835

Published: Jan. 1, 2025

Language: Английский

Citations

0
Methyltransferase-like 7B participates in bladder cancer via ACSL3 m6A modification in a ferroptosis manner DOI Creative Commons
Jiani He, Changming Dong,

Xiandong Song

et al.

Biology Direct, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 20, 2025

Language: Английский

Citations

0
Galactose-Induced Cataracts in Rats: A Machine Learning Analysis DOI Creative Commons

Ahmed Jasim Mahmood Al-Mashhadani,

Qiyong Gong,

Franko Shehaj

et al.

International Journal of Medical Sciences, Journal Year: 2025, Volume and Issue: 22(5), P. 1138 - 1149

Published: Feb. 10, 2025

Background: Rat models are widely used to study cataracts due their cost-effectiveness and prominent physiological genetic similarities humans The objective of this was identify genes involved in cataractogenesis galactose exposure rats. Methods: We analyzed four datasets from the Gene Expression Omnibus, including both ex vivo different rat strains. Feature selection tools were potentially relevant cataract-related gene expression. A decision tree algorithm implemented, its predictions interpreted using SHAP LIME. To validate expression levels, PCR conducted on six lenses cultured M199 medium induce cataract alone. Results: Using feature tools, key genes-PLAGL2, CMTM7, PCYT1B, NR1D2-were identified. Only PCYT1B significantly differentially expressed between control groups across datasets. model showed strong predictive performance, particularly LIME analyses revealed that CMTM7 had largest impact predictions. results did not show significant differences groups. Conclusion: trained an dataset could predict despite no found Given a small number samples, larger studies needed our findings.

Language: Английский

Citations

0
Upstream transcription factor 1 suppresses laryngeal squamous cell carcinoma progression through transcriptional activation of junctional adhesion molecule 3 DOI Creative Commons
Yue Jia, Jiaojiao Liu,

Yi-Han Lou

et al.

IUBMB Life, Journal Year: 2025, Volume and Issue: 77(3)

Published: March 1, 2025

Abstract Laryngeal squamous cell carcinoma (LSCC) exhibits aggressive growth, frequent recurrence, and a notable resistance to existing treatments. Building upon prior discoveries that identified junctional adhesion molecule 3 (JAM3) as critical tumor suppressor in LSCC, this study delves into the transcriptional regulation by upstream stimulatory factor 1 (USF1) its implications for LSCC pathogenesis. Employing dual‐luciferase assays chromatin immunoprecipitation–quantitative polymerase chain reaction (ChIP‐qPCR), we confirmed USF1's direct binding E‐box within JAM3 promoter, thereby enhancing expression AMC‐HN‐8 FD‐LSC‐1 cells. Complementary vitro vivo experiments corroborated USF1 overexpression markedly reduces aggressiveness, linked heightened activity. Further analysis, including Western blot immunohistochemistry of xenograft tissues, revealed increased JAM3, stimulated USF1, activates Hippo signaling pathway, underscoring role suppression. These findings position pivotal elements molecular framework suggesting their potential targets therapeutic intervention.

Language: Английский

Citations

0
Prognostic biomarker PSMD14 facilitates bladder cancer tumorigenesis and progression by regulating Nucleolin-YAP1 axis DOI
Yunfei Wu, Zhijie Xu,

R Wang

et al.

Translational Oncology, Journal Year: 2025, Volume and Issue: 55, P. 102370 - 102370

Published: March 23, 2025

Language: Английский

Citations

0
Reciprocal regulation between RACGAP1 and AR contributes to endocrine therapy resistance in prostate cancer DOI Creative Commons
Jia-Jia Wang, Hui Liu, Zeyuan Yu

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 19, 2024

Abstract Background Endocrine resistance driven by sustained activation of androgen receptor (AR) signaling pathway in advanced prostate cancer (PCa) is fatal. Characterization mechanisms underlying aberrant AR to search for potential therapeutic strategy particularly important. Rac GTPase-activating protein 1 (RACGAP1) one the specific proteins. As a novel tumor proto-oncogene, overexpression RACGAP1 was related occurrence various tumors. Methods Bioinformatics methods were used analyze relationship expression level between and as well activation. qRT-PCR western blotting assays performed assess AR/AR-V7 PCa cells. Immunoprecipitation immunofluorescence experiments conducted detect interaction co-localization AR/AR-V7. Gain- loss-of-function analyses investigate biological roles cells, using MTS colony formation assays. In vivo evaluate effect inhibition on growth. Results gene activated AR, which markedly upregulated patients with CRPC enzalutamide resistance. transcriptionally binding its promoter region. Reciprocally, nuclear bound N-terminal domain (NTD) both AR-V7, blocking their E3 ubiquitin ligase MDM2. Consequently, this prevented degradation ubiquitin-proteasome-dependent pathway. Notably, positive feedback loop contributed endocrine therapy CRPC. Combination cholesterol-conjugated RIG-I siRNA drugs targeting induced potent xenograft growth PCa. Conclusion summary, our results reveal that reciprocal regulation contributes These findings highlight combined treatment

Language: Английский

Citations

3
Assessing the role of statin therapy in bladder cancer: evidence from a Mendelian Randomization study DOI Creative Commons

Rongkang Li,

Guixiao Huang, Yunfei Li

et al.

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

Published: July 19, 2024

Background Statins, which are medications that lower lipid levels, extensively used to decrease cardiovascular disease risk. Recently, the use of statins in cancer prevention has attracted considerable interest. However, it is still unclear whether a causal effect on bladder cancer. Methods The two-sample Mendelian Randomization (MR) was performed infer relationship between statin therapy (atorvastatin, simvastatin, and rosuvastatin) Single-nucleotide polymorphisms (SNP)-based genome-wide association studies (GWAS) were gathered from UK Biobank, involving 462,933 participants. We acquired summary-level genetic data European cohort 175,121 individuals. inverse variance weighted (IVW) method main analytical technique used, supplemented by MR-Egger, median, mode, simple mode estimate effects. Additionally, sensitivity analyses conducted verify robustness reliability our findings. Results Based IVW analysis, we identified significant rosuvastatin decreased risk cancer, with analysis inferring substantial reduction odds (OR = 3.52E-19, 95% CI: 5.48E-32–2.26E-06, p 0.005). In contrast, results did not reveal statistically genetically estimated atorvastatin 7.42E-03, 6.80E-06–8.084, 0.169) or simvastatin 0.135, 0.008–2.330, 0.168) Conclusion investigated link using among population. Our findings indicated predicted associated whereas no effects observed for use.

Language: Английский

Citations

3