Deregulation of angiopoietin-like 4 slows ovarian cancer progression through vascular endothelial growth factor receptor 2 phosphorylation

Wu, Yuxian; Gao, Jinghai; Liu, Xiaojun

doi:10.1186/s12935-021-01865-4

Cited by 14 publications

(13 citation statements)

References 41 publications

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“…Consistent with other studies [ 23 – 26 ], we observed that ANGPTL4, PYGB and IRS2 were highly expressed in ovarian tumor tissues and patients with high expression of ANGPTL4, PYGB or IRS2 had significantly lower OS rates than patients with low expression of these factors. ANGPTL4, a secreted glycoprotein in the angiopoietin-like protein family, is involved in glucose and lipid metabolism and also plays an essential role in the prevention of apoptosis, induction of angiogenesis, inhibition of angiogenesis and facilitation of metastasis [ 23 , 32 , 33 ].…”

Section: Discussionsupporting

confidence: 92%

“…ANGPTL4, PYGB and IRS2 have been reported to be upregulated in OC, and this dysregulation promotes OC cell proliferation, invasion, migration and drug resistance [ 23 – 26 ]. However, the expression and function of ISG20 and SEH1L in OC have not yet been reported.…”

Section: Resultsmentioning

confidence: 99%

“…ANGPTL4, a secreted glycoprotein in the angiopoietin-like protein family, is involved in glucose and lipid metabolism and also plays an essential role in the prevention of apoptosis, induction of angiogenesis, inhibition of angiogenesis and facilitation of metastasis [ 23 , 32 , 33 ]. It was reported that deregulation of ANGPTL4 slows OC progression through VEGFR2 phosphorylation [ 26 ]. Besides, Yang et al found that the TAZ-ANGPTL4-NOX2 axis regulates ferroptosis and chemotherapy resistance in OC [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

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Identification and validation of a novel glycolysis-related gene signature for predicting the prognosis in ovarian cancer

Liu

Liang

et al. 2021

Cancer Cell Int

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Background Ovarian cancer (OC) is the most lethal gynaecological tumor. Changes in glycolysis have been proven to play an important role in OC progression. We aimed to identify a novel glycolysis-related gene signature to better predict the prognosis of patients with OC. Methods mRNA and clinical data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Genotype Tissue Expression (GTEx) database. The “limma” R package was used to identify glycolysis-related differentially expressed genes (DEGs). Then, a multivariate Cox proportional regression model and survival analysis were used to develop a glycolysis-related gene signature. Furthermore, the TCGA training set was divided into two internal test sets for validation, while the ICGC dataset was used as an external test set. A nomogram was constructed in the training set, and the relative proportions of 22 types of tumor-infiltrating immune cells were evaluated using the “CIBERSORT” R package. The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined by single-sample gene set enrichment analysis (ssGSEA) with the “GSVA” R package. Finally, the expression and function of the unreported signature genes ISG20 and SEH1L were explored using immunohistochemistry, western blotting, qRT-PCR, proliferation, migration, invasion and xenograft tumor assays. Results A five-gene signature comprising ANGPTL4, PYGB, ISG20, SEH1L and IRS2 was constructed. This signature could predict prognosis independent of clinical factors. A nomogram incorporating the signature and three clinical features was constructed, and the calibration plot suggested that the nomogram could accurately predict the survival rate. According to ssGSEA, the signature was associated with KEGG pathways related to axon guidance, mTOR signalling, tight junctions, etc. The proportions of tumor-infiltrating immune cells differed significantly between the high-risk group and the low-risk group. The expression levels of ISG20 and SEH1L were lower in tumor tissues than in normal tissues. Overexpression of ISG20 or SEH1L suppressed the proliferation, migration and invasion of Caov3 cells in vitro and the growth of xenograft tumors in vivo. Conclusion Five glycolysis-related genes were identified and incorporated into a novel risk signature that can effectively assess the prognosis and guide the treatment of OC patients.

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Identification and validation of a novel glycolysis-related gene signature for predicting the prognosis in ovarian cancer

Liu

Liang

et al. 2021

Cancer Cell Int

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“…ANGPTL4 is activated by hypoxia-inducible factor-1α (HIF-1α) and confers protection against hypoxiainduced apoptosis [34]. It is demonstrated that ANGPTL4 is overexpressed in OC and related to shorter relapse-free survival times in serous OC [35][36][37]. In addition, ANGPTL4 is significantly related to the poor prognosis of patients with non-small-cell lung cancer, lung adenocarcinoma, and cervical cancer [38][39][40].…”

Section: Discussionmentioning

confidence: 99%

Identification of Hypoxia Signature to Assess the Tumor Immune Microenvironment and Predict Prognosis in Patients with Ovarian Cancer

Wei

Liu

Wang

et al. 2021

International Journal of Endocrinology

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Background. The 5-year overall survival rate of ovarian cancer (OC) patients is less than 40%. Hypoxia promotes the proliferation of OC cells and leads to the decline of cell immunity. It is crucial to find potential predictors or risk model related to OC prognosis. This study aimed at establishing the hypoxia-associated gene signature to assess tumor immune microenvironment and predicting the prognosis of OC. Methods. The gene expression data of 378 OC patients and 370 OC patients were downloaded from datasets. The hypoxia risk model was constructed to reflect the immune microenvironment in OC and predict prognosis. Results. 8 genes (AKAP12, ALDOC, ANGPTL4, CITED2, ISG20, PPP1R15A, PRDX5, and TGFBI) were included in the hypoxic gene signature. Patients in the high hypoxia risk group showed worse survival. Hypoxia signature significantly related to clinical features and may serve as an independent prognostic factor for OC patients. 2 types of immune cells, plasmacytoid dendritic cell and regulatory T cell, showed a significant infiltration in the tissues of the high hypoxia risk group patients. Most of the immunosuppressive genes (such as ARG1, CD160, CD244, CXCL12, DNMT1, and HAVCR1) and immune checkpoints (such as CD80, CTLA4, and CD274) were upregulated in the high hypoxia risk group. Gene sets related to the high hypoxia risk group were associated with signaling pathways of cell cycle, MAPK, mTOR, PI3K-Akt, VEGF, and AMPK. Conclusion. The hypoxia risk model could serve as an independent prognostic indicator and reflect overall immune response intensity in the OC microenvironment.

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“…There is growing evidence that angiopoietin-like protein (ANGPTL) is associated with apoptosis, inflammation, tumor development, and metabolism [ 16 – 19 ]. Previous studies have illustrated that increased expression of Angptl4 in synovial fibroblasts within arthritic tissues [ 20 ] and angiopoietin family proteins contributes to the pathogenesis of OA [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Silencing of Angiopoietin-Like Protein 4 (Angptl4) Decreases Inflammation, Extracellular Matrix Degradation, and Apoptosis in Osteoarthritis via the Sirtuin 1/NF-κB Pathway

Chen

Pan

et al. 2022

Oxidative Medicine and Cellular Longevity

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Osteoarthritis (OA) is a frequently observed condition in aged people. OA cartilage is characterized by chondrocyte apoptosis, chondrocyte inflammation, and hyperactive catabolism of extracellular matrix. However, the specific molecular mechanisms remain unclear. Recent data has shown that Angptl4, a multifunctional cytokine, is involved in the regulation of inflammatory and apoptosis responses in different tissues. This study is aimed at defining the role of Angptl4 in the development of OA. We employed X-ray analysis, safranin O-fast green (S-O) staining, and hematoxylin staining to evaluate histomorphological characteristics in the knee joint of mice. Real-time quantitative polymerase chain reaction, Western blot assays, immunofluorescence staining, and enzyme-linked immunosorbent assays (ELISA) were performed to analyze the changes in gene and protein expression. Mechanically, our data demonstrated that Angptl4 knockdown improved the degradation of extracellular matrix and reduced TNF-α-mediated chondrocyte inflammation and apoptosis by suppressing sirtuin 1/NF-κB signaling pathway. In addition, animal studies showed that the suppression of Angptl4 expression might alleviate OA development. In conclusion, our findings revealed the underlying mechanisms of Angptl4 regulation in chondrocytes and its potential value in the treatment of OA.

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Deregulation of angiopoietin-like 4 slows ovarian cancer progression through vascular endothelial growth factor receptor 2 phosphorylation

Cited by 14 publications

References 41 publications

Identification and validation of a novel glycolysis-related gene signature for predicting the prognosis in ovarian cancer

Identification and validation of a novel glycolysis-related gene signature for predicting the prognosis in ovarian cancer

Identification of Hypoxia Signature to Assess the Tumor Immune Microenvironment and Predict Prognosis in Patients with Ovarian Cancer

Silencing of Angiopoietin-Like Protein 4 (Angptl4) Decreases Inflammation, Extracellular Matrix Degradation, and Apoptosis in Osteoarthritis via the Sirtuin 1/NF-κB Pathway

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