GPR176 enhances the epithelial-mesenchymal transition in gastric cancer cells by activating the PI3K/AKT/mTOR signaling pathway

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Gastric cancer is characterized by a high incidence and unfavorable prognosis. The exploration of novel molecular markers deeper understanding their mechanisms action hold the potential to offer fresh insights into gastric treatment. Leveraging TCGA-STAD GSE66254 datasets, this study conducted an analysis on relationship between GPR176 clinical pathological features. Furthermore, it was validated in patients from First Affiliated Hospital Guangxi Medical University. Cell migration invasion capabilities were evaluated through Transwell scratch assays. Western blot performed detect impact PI3K/AKT/mTOR signaling pathway. Nude mouse tumorigenesis experiments validate tumor growth in vivo. exhibited higher expression levels tissues, associated with poor prognosis cancer. Significant downregulation suppressed invasive migratory cells, concomitant inhibition PI3K EMT pathways. However, phenotypic changes induced its inhibitory effects could be reversed overexpression PIP5K1A. findings cell experiments, demonstrating that growth, while promoted growth. Similarly, after downregulation, pathways cells significantly inhibited, whereas upregulation led substantial activation. In conclusion, emerged as newly identified prognostic marker study. may promote activating

Language: Английский

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The oncogenic roles of GPR176 in ovarian cancer: a molecular target for aggressiveness and gene therapy

Journal of Obstetrics and Gynaecology, Journal Year: 2024, Volume and Issue: 44(1)

Published: June 4, 2024

Background At present, the discovery of new biomarkers is great significance for early diagnosis, treatment and prognosis assessment ovarian cancer. Previous findings indicated that aberrant G-protein-coupled receptor 176 (GPR176) expression might contribute to tumorigenesis subsequent progression. However, GPR176 molecular mechanisms in cancer had not been investigated.

Language: Английский

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Silencing immune-infiltrating biomarker CCDC80 inhibits malignant characterization and tumor formation in gastric cancer

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: June 13, 2024

Abstract Objective Tumor immune infiltration leads to poor prognosis of gastric cancer patients and seriously affects the life quality patients. This study was based on bioinformatics screen prognostic biomarkers in with high degree invasion cancer. Meanwhile, action biomarker CCDC80 explored by cell tumorigenesis experiments, provide reference for cure Methods Data sets clinical massage were collected from TCGA database GEO database. ConsensusClusterPlus used cluster 28 cells ssGSEA. R “Limma” package applied analyze differential mRNAs between Cluster 1 2. Differential expression genes screened single factor analysis. Stemness markers (SERPINF1, DCN, CCDC80, FBLN5, SPARCL1, CCL14, DPYSL3) identified genes. Prognostic value evaluated Differences genomic mutation tumor microenvironment assessed or low CCDC80. Finally, (HGC-27 MKN-45) selected evaluate silencing malignant characterization, macrophage polarization, formation. Results Bioinformatics analysis showed that as a stemness marker, significantly overexpressed also related invasion. up-expressed Silencing inhibited characterization subcutaneous formation cells. High positive correspondence M2 polarization promoted M1 tissues. In addition, likely have mutations CDH1, ACTRT1, GANAB, CDH10 High-CCDC80 group. Conclusion cancer, could effectively inhibit

Language: Английский

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The promoting effects of GPR176 expression on proliferation, chemoresistance, lipogenesis and invasion of oesophageal cancer

Journal of Cancer Research and Clinical Oncology, Journal Year: 2023, Volume and Issue: 149(16), P. 14641 - 14655

Published: Aug. 16, 2023

Abstract Purpose As a member of the G-protein-coupled receptor 1 family, 176 (GPR176) gene encodes glycosylated protein made up 515 amino acids. The current study was performed to evaluate impact GPR176 on clinicopathology and prognosis oesophageal cancer, as well uncover its molecular mechanisms. Methods Bioinformatics clinical tissue samples were used detect expression clinicopathological significance in cancer. expression, proliferation, migration invasion, apoptosis lipid droplet formation cancer phenotypic readouts. Results Here, RT-PCR bioinformatic analyses revealed that mRNA significantly higher than normal mucosa (p < 0.05). associated with low weight BMI, T stage, N histological grade favourable outcome differential genes involved digestion absorption, extracellular matrix constituent, endoplasmic reticulum lumen, among others GPR176-related classified being oxidoreductase activity, actin myosin complexes, localisation transport, knockdown suppressed anti-apoptotic anti-pyroptotic properties, migration, chemoresistance cells 0.05), while ACC1 ACLY overexpression reversed inhibitory effects silencing chemoresistance. Conclusion These findings indicated upregulated might be carcinogenesis subsequent progression, aggressiveness, induced by ACC1- ACLY-mediated lipogenesis assembly.

Language: Английский

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GPR176 promotes fibroblast-to-myofibroblast transition in organ fibrosis progression

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2024, Volume and Issue: 1871(7), P. 119798 - 119798

Published: July 22, 2024

Fibrosis is characterized by excessive deposition of extracellular matrix proteins, particularly collagen, caused myofibroblasts in response to chronic inflammation. Although G protein-coupled receptors (GPCRs) are among the targets current antifibrotic drugs, no drug has yet been approved stop fibrosis progression. Herein, we aimed identify GPCRs with profibrotic effects. In gene expression analysis mouse lungs induced fibrosis, eight were identified, showing a >2-fold increase mRNA after induction. Among them, focused on Gpr176 owing its significant correlation myofibroblast marker α-smooth muscle actin (αSMA), factor transforming growth β1 (TGFβ1), and collagen human lung database. Similar model, increased was also observed other organs affected including kidney, liver, heart, suggesting role across various organs. Furthermore, fibroblasts abundantly expressed compared alveolar epithelial cells, endothelial macrophages fibrotic lung. GPR176 unaffected TGFβ1 stimulation rat renal fibroblast NRK-49 whereas knockdown siRNA reduced TGFβ1-induced αSMA, fibronectin, as well Smad2 phosphorylation. This suggested that regulates activation. Consequently, acts manner, inhibiting activity could potentially prevent differentiation improve fibrosis. Developing inverse agonist or allosteric modulator promising therapeutic approach for

Language: Английский

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High expression of GPR176 predicts poor prognosis of gastric cancer patients and promotes the proliferation, migration, and invasion of gastric cancer cells

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: June 8, 2023

Abstract G-protein-coupled receptors (GPCRs) are the most prominent family of cell surface receptors, which can regulate various biological functions and play an essential role in many diseases. GPR176 is a member GPCRs has been rarely studied cancer. We aim to investigate diagnostic prognostic value gastric cancer (GC) explore its potential mechanism. Through TCGA database real-time quantitative PCR, we found that expression level was significantly increased GC had good diagnosis prognosis GC. Vitro experiments revealed could promote proliferation, migration, invasion cells may be involved regulating multiple tumors immune-related signaling pathways. In addition, associated with immune infiltration affect efficacy patients. summary, high poor prognosis, more robust infiltration, worse immunotherapy patients, suggesting biomarker for cells.

Language: Английский

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Conversion surgery for stage IV gastric cancer after third-line immunotherapy: a case report

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Dec. 6, 2024

The 5-year overall survival rate for stage IV gastric cancer is lower than 10%, despite the development of systemic therapy. Conversion surgery has shown to improve outcomes in patients with durable clinical response on chemotherapy. We report a case patient, who underwent conversion after pembrolizumab third-line setting cancer. patient did not have recurrence 22 months surgery.

Language: Английский

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