Downregulation of sorting nexin 10 is associated with overexpression of miR-30d during liver cancer progression in rats

Cervantes-Anaya, Nancy; Ponciano-Gómez, Alberto; López-Álvarez, Guadalupe S.; González-Reyes, Christian; Hernández-García, Sergio; Cabañas-Cortés, María Asunción; Garrido-Guerrero, José Efraín; Villa‐Treviño, Saúl

doi:10.1177/1010428317695932

Cited by 17 publications

(14 citation statements)

References 27 publications

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“…Supporting our patient data, a recent report showed that miR‐30d expression was high in hypoxic CRC cell lines and in primary tumours from patients who failed adjuvant therapy (presumably by metastatic progression, but not specified [33]). In hepatocellular carcinoma, miR‐30d was shown to be highly expressed [49–51] and promote intrahepatic tumour cell invasion and implant tumours [49]. Interestingly, the great majority of the metastatic cases in the present study had dissemination to the liver, suggesting that circulating exosomal miR‐30d‐5p from their primary tumours may have contributed to this organ‐specificity of metastasis [52].…”

Section: Discussionmentioning

confidence: 86%

An experimental strategy unveiling exosomal microRNAs 486‐5p, 181a‐5p and 30d‐5p from hypoxic tumour cells as circulating indicators of high‐risk rectal cancer

Bjørnetrø

Redalen

Meltzer

et al. 2019

J of Extracellular Vesicle

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Tumour hypoxia contributes to poor treatment outcome in locally advanced rectal cancer (LARC) and circulating extracellular vesicles (EVs) as potential biomarkers of tumour hypoxia and adverse prognosis have not been fully explored. We examined EV miRNAs from hypoxic colorectal cancer cell lines as template for relevant miRNAs in LARC patients participating in a prospective biomarker study (NCT01816607). Five cell lines were cultured under normoxia (21% O2) or hypoxia (0.2% O2) for 24 h, and exosomes were isolated by differential ultracentrifugation. Using a commercial kit, exosomes were precipitated from 24 patient plasma samples collected at the time of diagnosis. Exosome size distribution and protein cargo were determined by cryo-electron microscopy, nanoparticle tracking analysis, immunoblotting and flow cytometry. The vesicles harboured strong cell line-specific miRNA profiles with 35 unique miRNAs differentially expressed between hypoxic and normoxic cells. Six of these miRNAs were considered candidate-circulating markers of tumour hypoxia in the patients based on the frequency or magnitude of variance in hypoxic versus normoxic cell line experiments and prevalence in patient plasma. Of these, low plasma levels of exosomal miR-486-5p and miR-181a-5p were associated with organ-invasive primary tumour (p = 0.029) and lymph node metastases (p = 0.024), respectively, both attributes of adverse LARC prognosis. In line with this, the plasma level of exosomal miR-30d-5p was elevated in patients who experienced metastatic progression (p = 0.036). Our strategy confirmed that EVs from colorectal cancer cell lines were exosomes containing the oxygen-sensitive miRNAs 486-5p, 181a-5p and 30d-5p, which were retrieved as circulating markers of high-risk LARC.

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Section: Discussionmentioning

confidence: 86%

An experimental strategy unveiling exosomal microRNAs 486‐5p, 181a‐5p and 30d‐5p from hypoxic tumour cells as circulating indicators of high‐risk rectal cancer

Bjørnetrø

Redalen

Meltzer

et al. 2019

J of Extracellular Vesicle

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“…SNX10 is believed to be a regulator of macrophage polarization ( 67 ). SNX10 has also been shown to have potential role in liver cancer by suppressing microRNA-30d ( 68 ). CCBP2 and GAS7 are two other genes inhibited by U-STAT1.…”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of Autoimmune Regulator-Regulated Genes in Human and Murine Models: A Novel Human Model Provides Insights on the Role of Autoimmune Regulator in Regulating STAT1 and STAT1-Regulated Genes

et al. 2018

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Autoimmune regulator (AIRE) regulates promiscuous expression of tissue-restricted antigens in medullary epithelial cells (mTEC) of the thymus. To understand the diverse effects of AIRE, it is crucial to elucidate the molecular mechanisms underlying the process of AIRE-regulated gene expression. In this study, we generated a recombinant AIRE expression variant of the TEC 1A3 human cell line, TEC 1A3 AIREhi, to determine genes targeted by AIRE, and using microarray analysis, we identified 482 genes showing significant differential expression (P < 0.05; false discovery rate <5%), with 353 upregulated and 129 downregulated by AIRE expression. Microarray data were validated by quantitative PCR, confirming the differential expression of 12 known AIRE-regulated genes. Comparison of AIRE-dependent differential expression in our cell line model with murine datasets identified 447 conserved genes with a number of transcription regulatory interactions, forming several key nodes, including STAT1, which had over 30 interactions with other AIRE-regulated genes. As STAT1 mutations cause dominant chronic mucocutaneous candidiasis and decreased STAT1 levels in monocytes of autoimmune polyglandular syndrome 1 (APS-1) patients, it was important to further characterize AIRE–STAT1 interactions. TEC 1A3AIREhi were treated with the STAT1 phosphorylation inhibitors fludarabine and LLL3 showed that phosphorylated STAT1 (p-STAT1) was not responsible for any of the observed differential expression. Moreover, treatment of TEC 1A3 AIREhi with STAT1 shRNA did not induce any significant variation in the expression of unphosphorylated STAT1 (U-STAT1) downstream genes, suggesting that these genes were directly regulated by AIRE but not via U-STAT1. The novel model system we have developed provides potential opportunities for further analysis of the pathogenesis of (APS-1) and the wider roles of the AIRE gene.

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“…Sorting nexin 10 (SNX10), a protein maintaining endosome/lysosome homeostasis a tumor, can suppress the tumorigenesis and progression of colorectal cancer, liver cancer and stomach cancer (51,52). Cervantes-Anaya N et al demonstrated SNX10/V-ATPase pathway regulated ciliogenesis in vitro and in vivo (52). Prostaglandin D synthase (PTGDS), which catalyzes the conversion of prostaglandin H2 into prostaglandin D2 (PGD2), has been intensely studied (53).…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of two novel genes SNX10 and PTGDS for cervical squamous cell carcinoma: an integrated bioinformatic analysis

Jiang¹,

Cao²,

Gao³

et al. 2020

Preprint

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KEYWORDSCervical squamous cell carcinoma, methylation prognosis risk model SNX10, PTGDS in females (1). Despite pre-cancerous screening and emerging treatments, CC remains the primary cause of death in women in developing countries (2). When CC becomes metastasizes and recurs, the prognosis gets even worse. Therefore, it is of great significance to establish target treatments of CC based on its to-be-clarified molecular mechanism.Gene expression microarray, as an efficient means of acquiring large-scale genetic data, has been mostly used to study gene expression profiling in many human cancers. New methods and good foreground are provided by microarrays for studying tumor-associated genes, molecular targeting, molecular prediction and therapy. The integration of databases containing gene expression chips allows in-depth study of molecular mechanisms(3, 4).Up to now, the expression profiles of thousands of differentially expressed genes (DEGs) in CC have been researched (5-7). However, the results on some mRNAs are inconsistent. Here we use an unbiased approach to solve this problem.In our study, we screened DEGs from four profiles downloaded from GEO. PPI network was built by STRING Database and hub modules selected via plug-in MCODE. CMap was used to find potential molecules associated with CC. We also validated hub genes with GEO datasets, GEPIA, immunohistochemistry and ONCOMINE. ROC curve analysis and GESA were also done to tease out the significance of hub genes. The flow chart of this research was displayed in Fig. 1. Methods Screening DEGsKeywords "cervical cancer geo accession" were put in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) and the gene expression profiles of GSE6791, GSE63514, GSE39001 and GSE9750 were downloaded. The dataset information is shown in Table 1. We processed unqualified data by R package. The data is calibrated, standardized and log2-transformed.Gene expression analysis was performed using the limma(8) package in the Bioconductor package.Relevant codes were placed into R. We selected four microarray datasets and analyzed them with limma. The |log2fold change (FC)| > 2 and adjusted p < 0.05 were set as cutoffs. RRA package was download (http://cran.r-project.org/)(9) and R was used for running the instruction code.

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Downregulation of sorting nexin 10 is associated with overexpression of miR-30d during liver cancer progression in rats

Cited by 17 publications

References 27 publications

An experimental strategy unveiling exosomal microRNAs 486‐5p, 181a‐5p and 30d‐5p from hypoxic tumour cells as circulating indicators of high‐risk rectal cancer

An experimental strategy unveiling exosomal microRNAs 486‐5p, 181a‐5p and 30d‐5p from hypoxic tumour cells as circulating indicators of high‐risk rectal cancer

Meta-Analysis of Autoimmune Regulator-Regulated Genes in Human and Murine Models: A Novel Human Model Provides Insights on the Role of Autoimmune Regulator in Regulating STAT1 and STAT1-Regulated Genes

Prognostic value of two novel genes SNX10 and PTGDS for cervical squamous cell carcinoma: an integrated bioinformatic analysis

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