EPAS1 promotes peritoneal carcinomatosis of non-small-cell lung cancer by enhancing mesothelial–mesenchymal transition

Zhen, Qiang; Zhang, Yaxiao; Gao, Lina; Wang, Renfeng; Chu, Weiwei; Zhao, Xiaojie; Li, Zhe; Li, Huixian; Zhang, Bing; Lv, Baolei; Liu, Jia‐Bao

doi:10.1007/s00066-020-01665-1

Cited by 17 publications

(14 citation statements)

References 37 publications

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“…Low EPAS1 expression in cancer, including LUAD, has been reported [ 30 ]. In NSCLC, EPAS1 can promote peritoneal carcinomatosis by enhancing the mesothelial-mesenchymal transition [ 31 ]. In the present study, downregulation of EPAS1 was further confirmed and EPAS1 was associated with favorable prognosis for LUAD, indicating that it may be a promising biomarker and therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

Decreased HLF Expression Predicts Poor Survival in Lung Adenocarcinoma

Wang

Chen

et al. 2021

Med Sci Monit

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Background Lung adenocarcinoma (LUAD) is a type of non-small cell carcinoma. Its pathogenesis is being explored and there is no cure for the disease. Material/Methods The Gene Expression Omnibus (GEO) was searched to obtain data on expression of messenger RNA. GEO2R, an interactive web tool, was used to calculate the differentially expressed genes (DEGs) in LUAD. All the DEGs from different datasets were imported into VENNY 2.1 ( https://bioinfogp.cnb.csic.es/tools/venny/index.html ) to identify the intersection of the DEGs. An online analysis tool, the Database for Annotation, Visualization, and Integrated Discovery (DAVID), was used to help understand the biological meaning of DEG enrichment in LUAD. Cytoscape 3.7.2 was used to perform centrality analysis and visualize hub genes and related networks. Furthermore, the prognostic value of the hub genes was evaluated with the Kaplan-Meier plotter survival analysis tool. Results The GEO database was used to obtain RNA sequencing information for LUAD and normal tissue from the GSE118370, GSE136043, and GSE140797 datasets. A total of 376 DEGs were identified from GSE118370, 248 were identified from GSE136403, and 718 DEGs were identified from GSE140797. The 10 genes with the highest degrees of expression – the hub genes – were CAV1, TEK, SLIT2, RHOJ, DGSX, HLF, MEIS1, PTPRD, FOXF1 , and ADRB2 . In addition, Kaplan-Meier survival evaluation showed that CAV1, TEK, SLIT2, HLF, MEIS1, PTPRD, FOXF1 , and ADRB2 were associated with favorable outcomes for LUAD. Conclusions CAV1, TEK, SLIT2, HLF, MEIS1, PTPRD, FOXF1 , and ADRB2 are hub genes in the DEG interaction network for LUAD and are involved in the development of and prognosis for the disease. The mechanisms underlying these genes should be the subject of further studies.

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Section: Discussionmentioning

confidence: 99%

Decreased HLF Expression Predicts Poor Survival in Lung Adenocarcinoma

Wang

Chen

et al. 2021

Med Sci Monit

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“…EPAS1 is a transcription factor that is responsible for inducing genes associated with cell survival under hypoxic conditions 41 . Studies have shown that EPAS1 promotes peritoneal carcinogenesis in NSCLC patients by enhancing MMT (mesothelial-mesenchymal transition), therefore, it is a potential prognostic marker or therapeutic target for NSCLC 17 . Bioinformatics analysis of miR-182-5p revealed that EPAS1, PRKCE (protein kinase C epsilon), NR3C1 (nuclear receptor subfamily 3 group C member 1), and RHOB are the primary genes in the protein-protein interaction (PPI) network of lung squamous cell carcinoma 18 .…”

Section: Discussionmentioning

confidence: 99%

“…It plays essential roles in cell survival and invasion through E-cadherin, Vimentin, Ki-67, CD31 14 , and VEGFA 15 16 . It has been associated with several human cancers 17 . Studies have reported that EPAS1 is the primary target gene of miR-182-5p 18 .…”

Section: Introductionmentioning

confidence: 99%

MiR-182-5p promotes the Metastasis and Epithelial-mesenchymal Transition in Non-small Cell Lung Cancer by Targeting EPAS1

Yang¹,

Yin²,

Bi³

et al. 2021

J. Cancer

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Background: Dysregulation of microRNAs (miRNAs) is associated with the pathogenesis of non-small cell lung cancer (NSCLC). However, the mechanisms through which miR-182-5p regulate NSCLC progression have not been established. This study aimed at evaluating the expression levels of miR-182-5p in human NSCLC and its function in lung cancer cells. Endothelial PAS Domain-containing protein 1 (EPAS1; also referred to as hypoxia-inducing factor 2A, HIF-2α) is a transcription factor that is responsible for induction of genes related to cell survival under hypoxia conditions. Hypoxia, an inherent feature of solid tumors, is associated with aggressive phenotypes, as well as resistance to radiotherapy and chemotherapy, which predict metastasis and poor prognosis. Methods: The Cancer Genome Atlas (TCGA) dataset was used to investigate the association between miR-182-5p expression and clinicopathological characteristics as well as prognosis of NSCLC patients. Target genes of miR-182-5p were identified using the PITA, miRmap, microT, miRanda, PicTar, and TargetScan prediction tools. Transwell assays were performed to determine the potential functions of miR-182-5p in lung cancer cells. Luciferase reporter assays were performed to analyze regulation of the putative target of miR-182-5p while western blot assays were used to validate the luciferase results. Results: miR-182-5p was found to be upregulated in NSCLC tissues and acted as an independent prognostic factor for tumor recurrence in NSCLC patients. Functionally, overexpression of miR-182-5p promoted lung cancer cell migration and invasion. Genome-wide gene expression analysis and luciferase report assays revealed that EPAS1 is a direct target of miR-182-5p. EPAS1 was negatively correlated with miR-182-5p expression in NSCLC tissues. Univariate and multivariate survival analyses identified EPAS1 as an independent prognostic factor for overall survival (OS) in NSCLC. Conclusions: These findings imply that miR-182-5p promotes NSCLC progression by targeting EPAS1 and is, therefore, a potential indicator of tumor recurrence in NSCLC patients.

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“…Interestingly, it was reported that endothelial PAS domain protein 1 (EPAS1) is also activated under hypoxic conditions. EPAS1 overexpression is an obvious finding in cancer and can enhance cancer metastasis via EMT induction [ 276 , 277 ]. The polyethylenimine-poly(lactide-coglycolide) (PLGA)/poloxamer nanoparticles loaded with EPAS1 siRNA have been applied for PC therapy.…”

Section: Co-delivery Systemsmentioning

confidence: 99%

Pre-Clinical and Clinical Applications of Small Interfering RNAs (siRNA) and Co-Delivery Systems for Pancreatic Cancer Therapy

Mirzaei

Gholami

Ang

et al. 2021

Cells

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Pancreatic cancer (PC) is one of the leading causes of death and is the fourth most malignant tumor in men. The epigenetic and genetic alterations appear to be responsible for development of PC. Small interfering RNA (siRNA) is a powerful genetic tool that can bind to its target and reduces expression level of a specific gene. The various critical genes involved in PC progression can be effectively targeted using diverse siRNAs. Moreover, siRNAs can enhance efficacy of chemotherapy and radiotherapy in inhibiting PC progression. However, siRNAs suffer from different off target effects and their degradation by enzymes in serum can diminish their potential in gene silencing. Loading siRNAs on nanoparticles can effectively protect them against degradation and can inhibit off target actions by facilitating targeted delivery. This leads to enhanced efficacy of siRNAs in PC therapy. Moreover, different kinds of nanoparticles such as polymeric nanoparticles, lipid nanoparticles and metal nanostructures have been applied for optimal delivery of siRNAs that are discussed in this article. This review also reveals that how naked siRNAs and their delivery systems can be exploited in treatment of PC and as siRNAs are currently being applied in clinical trials, significant progress can be made by translating the current findings into the clinical settings.

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EPAS1 promotes peritoneal carcinomatosis of non-small-cell lung cancer by enhancing mesothelial–mesenchymal transition

Cited by 17 publications

References 37 publications

Decreased HLF Expression Predicts Poor Survival in Lung Adenocarcinoma

Decreased HLF Expression Predicts Poor Survival in Lung Adenocarcinoma

MiR-182-5p promotes the Metastasis and Epithelial-mesenchymal Transition in Non-small Cell Lung Cancer by Targeting EPAS1

Pre-Clinical and Clinical Applications of Small Interfering RNAs (siRNA) and Co-Delivery Systems for Pancreatic Cancer Therapy

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