Overexpression of NREP Promotes Migration and Invasion in Gastric Cancer Through Facilitating Epithelial-Mesenchymal Transition

Liu, Yuan-jie; Zeng, Shuhong; Hu, Yi-dou; Zhang, Yonghua; Li, Jie-Pin

doi:10.3389/fcell.2021.746194

Cited by 15 publications

(13 citation statements)

References 71 publications

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“…NREP is highly expressed in embryo and mouse brain, and can participate in cell proliferation, migration, differentiation and other biological functions (Pan et al, 2002;Yao et al, 2015). NREP plays an important role in the progression of malignant tumors and may be involved in the activation of cancer-related fibroblasts and epithelial-mesenchymal transition (EMT), both of which are mediated by transforming growth factor-β1 (Liu et al, 2021). In addition, Liu et al (2021) reported that the expression of NREP was positively correlated with the Frontiers in Genetics frontiersin.org abundance of M2 macrophages, which are potent immunosuppressors, suggesting that NREP is overexpressed in GC and affects the prognosis.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analyses for the identification of tumor antigens and immune subtypes of gastric adenocarcinoma

et al. 2022

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Background: Although mRNA vaccines have been effective against multiple cancers, their efficacy against stomach adenocarcinoma (STAD) remains undefined. Immunotyping can indicate the comprehensive immune status in tumors and their immune microenvironment, which is closely associated with therapeutic response and vaccination potential. The aim of this study was to identify potential antigens in STAD for mRNA vaccine development, and further distinguish immune subtypes of STAD to construct an immune landscape for selecting suitable patients for vaccination.Methods: The gene expression and clinicopathological features of patients with gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Program (GTEx). 729 samples from GSE66229 and GSE84437 were downloaded through GEO and were used as the validation cohorts. Differential gene expression, genetic alterations and prognosis were analyzed using the R package, cBioPortal program and Kaplan-Meier. The relationship between tumor antigens and immune cells was evaluated and plotted by TIMER. ConsensusClusterPlus was used for consistency matrix construction and data clustering, and graph learning-based dimensional reduction was used to depict immune landscape. WGCNA was used to estimate the relationship between the color modules and immune subtypes.Results: Two overexpressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in STAD, including RAI14 and NREP. The immune subtypes showed distinct molecular, cellular and clinical characteristics. IS1 and IS2 exhibited immune-activated phenotypes and correlated to better survival compared to IS3, while IS3 tumors was immunologically cold. Immunogenic cell death modulators, immune checkpoints, and CA125, and CEA were also differentially expressed among the three immune subtypes. Finally, the immune landscape of STAD showed a high degree of heterogeneity between individual patients.Conclusion: RAI14 and NREP are potential antigens for developing anti-STAD mRNA vaccine, and patients with IS1 and IS3 tumors may be suitable for vaccination.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics analyses for the identification of tumor antigens and immune subtypes of gastric adenocarcinoma

et al. 2022

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“…The M2 polarization of macrophages has been confirmed to promote the progression of malignant tumors. 34 , 35 In addition, Akt and STAT6 have been reported to promote M2 polarization. 36 , 37 In the present study, exosomes overexpressing LOC441178 inactivated Akt/STAT6 signaling.…”

Section: Discussionmentioning

confidence: 99%

Tumor cell-derived exosomal lncRNA LOC441178 inhibits the tumorigenesis of esophageal carcinoma through suppressing macrophage M2 polarization

Chen

Chen²,

Hu³

et al. 2022

Eur J Histochem

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Esophageal carcinoma (EC) is a highly malignant type of tumor. In a previous study, the authors found that long non-coding RNA (lncRNA) LOC441178 inhibited the tumorigenesis of EC. Moreover, exosomes derived from tumor cells containing lncRNAs were found to play a key role in the tumor environment; however, whether exosomes can affect the tumor microenvironment by carrying LOC441178 remains unclear. Thus, the present study aimed to clarify this. In order to assess the effects of exosomal LOC441178 in EC, cell invasion and migration were examined using the Transwell assay. Exosomes were identified using transmission electron microscopy, western blot analysis and nanoparticle tracking analysis. Furthermore, macrophage surface makers (CD206 and CD86) were analyzed using flow cytometry. Moreover, a subcutaneous xenograft mouse model was constructed to assess the role of TE-9 cells-derived exosomal LOC441178 in EC. The results revealed that LOC441178 overexpression notably suppressed the metastasis of EC cells. In addition, exosomes were successfully isolated from EC cells, and LOC441178 level was upregulated in exosomes derived from LOC441178-overexpressed EC cells. Exosomal LOC441178 also suppressed macrophage M2 polarization, and the polarized macrophages decreased EC cell invasion. Exosomes containing LOC441178 notably inhibited the growth of EC in mice. On the whole, the present study demonstrated that the delivery of LOC441178 by EC cell-secreted exosomes inhibited the tumorigenesis of EC by suppressing the polarization of M2 macrophages. These findings may provide a new theoretical basis for discovering new strategies against EC.

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“…Immunofluorescence staining followed the method described in our previous study [ 30 ]. Staining was examined by epifluorescence microscopy (model BX60-32FB2-A03; Olympus Corp.), and different filters were used for capturing images using an Olympus DP50 camera.…”

Section: Methodsmentioning

confidence: 99%

Identification of COX4I2 as a hypoxia-associated gene acting through FGF1 to promote EMT and angiogenesis in CRC

Liu

Zeng

et al. 2022

Cell Mol Biol Lett

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Background Current evidence suggests that the hypoxic tumor microenvironment further aggravates tumor progression, leading to poor therapeutic outcomes. There is as yet no biomarker capable of evaluating the hypoxic state of the tumor. The cytochrome c oxidase (COX) subunit is crucial to the mitochondrial respiratory chain. Methods We investigated the potential oncogenic role of COX subunit 4 isoform 2 gene (COX4I2) in colorectal cancer (CRC) by least absolute shrinkage and selection operator (LASSO) and COX regression analysis to examine whether COX4I2 overexpression can predict colorectal cancer (CRC) prognosis. The association of COX4I2 levels with clinical features and its biological actions were evaluated both in vitro and in vivo. Results Our analysis showed that elevated COX4I2 levels were correlated with poor clinical outcomes. We also observed that that COX4I2 may be involved in epithelial-mesenchymal transition, activation of cancer-related fibroblasts and angiogenesis in relation to fibroblast growth factor 1. Conclusions The COX4I2 level may be a predictor of outcome in CRC and may represent a novel target for treatment development. Graphical Abstract

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Overexpression of NREP Promotes Migration and Invasion in Gastric Cancer Through Facilitating Epithelial-Mesenchymal Transition

Abstract: Graphical Abstract(A) Study Flow chart, (B) Diagram depicting the regulation mechanism of NREP in the tumorigenesis of gastric cancer.

Cited by 15 publications

References 71 publications

Bioinformatics analyses for the identification of tumor antigens and immune subtypes of gastric adenocarcinoma

Bioinformatics analyses for the identification of tumor antigens and immune subtypes of gastric adenocarcinoma

Tumor cell-derived exosomal lncRNA LOC441178 inhibits the tumorigenesis of esophageal carcinoma through suppressing macrophage M2 polarization

Identification of COX4I2 as a hypoxia-associated gene acting through FGF1 to promote EMT and angiogenesis in CRC

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