Visfatin facilitates esophageal cancer migration by suppressing miR-3613-5p expression and promoting VEZF1/VCAN production
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE298998 | GEO | 2025/06/09
REPOSITORIES: GEO
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Project description:Visfatin facilitates esophageal cancer migration by suppressing miR-3613-5p expression and promoting VEZF1/VCAN production
| PRJNA1272084 | ENA
Project description:Lung cancer is an intrinsically highly metastatic disease and the leading cause of cancer-related deaths worldwide. Although discovery of molecular aberrations in lung adenocarcinomas has led to development of effective targeted therapies, corresponding “drivers” in lung squamous carcinomas (LUSC) have not materialized. Extensive molecular profiling has revealed LUSC tumors have non-recurrent somatic mutations and are largely driven by copy number alterations. Because microRNAs (miRs) play increasingly important roles in regulating metastasis-relevant pathways, we evaluated whether miRs can regulate LUSC progression. By integrating bioinformatics of the Cancer Genome Atlas (TCGA) with novel, highly metastatic LUSC models, we found that miR-671-5p is a key inhibitor of LUSC metastasis. Surprisingly, miR-671-5p regulates LUSC metastasis by inhibiting a circular RNA (circRNA), CDR1as. Although the putative function of CDR1as is through miR-7 sponging, we found miR-671-5p more potently silences an axis of CDR1as and its anti-sense transcript, cerebellar degeneration related antigen 1 (CDR1). To our knowledge, no function of CDR1 has ever been described. We found loss of CDR1as and CDR1 significantly inhibited LUSC metastases. Intriguingly, CDR1 was strongly associated with an epithelial-mesenchymal transition (EMT) program in LUSC tumors, and was sufficient to promote metastases, increased migration and substrate-independent survival, known as anoikis-resistance. CDR1, which directly interacts with AP1 and COPI subunits, no longer promoted migration and anoikis-resistance upon blockade of Golgi trafficking. Our findings reveal a miR/circRNA axis that regulates LUSC metastases through an enigmatic protein, CDR1.
2021-09-08 | PXD012286 | Pride
Project description:Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer. MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in gene regulation and their dysregulation is associated with many diseases. In this study, we determined the expression and function of miR-590-3p in EOC. We found that miR-590-3p levels were higher in high-grade carcinoma when compared to low-grade or tumours with low malignant potential. Interestingly, plasma levels of miR-590-3p were significantly higher in EOC patients than in subjects with benign gynaecological disorders. Transient transfection of miR-590-3p mimics, or stable transfection of mir-590, increased cell growth, migration, and invasion. In vivo studies revealed that mir-590 accelerated tumour growth and metastasis. Using a cDNA microarray, we identified Forkhead box A2 (FOXA2) and Versican (VCAN) as a top downregulated and a top upregulated gene, respectively, by mir-590. We showed that miR-590-3p targeted FOXA2 3’ UTR to suppress its expression. In addition, knockdown of FOXA2 by siRNAs or knockout of FOXA2 by CRISPR/Cas9 enhanced cell proliferation, migration, and invasion. Overexpression of FOXA2 decreased, while knockout of FOXA2 increased, VCAN mRNA and protein levels and ChIP-qPCR revealed that FOXA2 binds to VCAN promoter. Interrogation of the TCGA ovarian cancer database revealed a negative relationship between FOXA2 and VCAN mRNA levels in EOC tumours and that high FOXA2/low VCAN mRNA levels in tumours were positively correlated with patient survival. Finally, overexpression of FOXA2 or silencing of VCAN reversed the effects of mir-590. These findings demonstrate that miR-590-3p promotes EOC development via a novel FOXA2-VCAN pathway.
2018-04-21 | GSE113440 | GEO
Project description:Cellular directed migration is critical to invasion-metastasis cascade of cancer cells. We used in vitro transwell model to screen two esophageal cancer cell lines (KYSE30/180) and obtained two pairs of subpopulations with distinct motility ability. Then we used microarrays to detail the differentially expressed genes and microRNAs between these two cell sublines (30U/D and 180U/D) to identify those responsible for ESCC motility.
2015-12-31 | GSE67508 | GEO
Project description:Cellular directed migration is critical to invasion-metastasis cascade of cancer cells. We used in vitro transwell model to screen two esophageal cancer cell lines (KYSE30/180) and obtained two pairs of subpopulations with distinct motility ability. Then we used microarrays to detail the differentially expressed genes and microRNAs between these two cell sublines (30U/D and 180U/D) to identify those responsible for ESCC motility. KYSE30/180 cells were subject to four successive selections using transwell (CORNING, USA). Subpopulations penetrated through membrane (D) or not (U) were harvested respectively for RNA extraction and hybridization on Affymetrix genome and LC Sciences microRNA microarrays simultaneously.
2015-12-31 | E-GEOD-67508 | biostudies-arrayexpress
Project description:Bone morphogenetic protein 4 (BMP4) is a remarkably powerful inhibitor of breast cancer cell proliferation, but is also able to induce breast cancer cell migration in certain cellular contexts. Previous data demonstrate that BMP4 controls the transcription of a variety of protein coding genes, but not much is known about microRNAs (miRNA) regulated by BMP4. In this study, miRNA expression patterns following BMP4 treatment were determined in one mammary epithelial and seven breast cancer cell lines using microarrays. The analysis identified 20 to 128 differentially expressed miRNAs in individual cell lines with emphasis on upregulation over downregulation. Four miRNAs (miR-16-5p, miR-106b-5p, miR-23a-3p and miR-23b-3p) were commonly induced in a subset of breast cancer cells upon BMP4 treatment and inhibition of their expression resulted in an increase in BT-474 cell number, indicating that they possess tumor suppressive properties. Yet no major change was detected when the cells were simultaneously treated with BMP4, and thus these miRNAs do not act as the main mediators of BMP4-induced growth reduction. MiR-16-5p and miR-106b-5p were elevated in MDA-MB-231 cells that respond to BMP4 with increased migration. Their inhibition, in combination with BMP4 treatment, resulted in enhanced MDA-MB-231 cell migration, suggesting that miR-16-5p and miR-106b-5p are engaged in BMP4-induced motility. Taken together, we have shown for the first time that in breast cancer cells BMP4 induces variable miRNA expression patterns.
2015-12-01 | GSE70480 | GEO
Project description:microRNA-7-5p (miR-7-5p) is an established tumor suppressor in multiple cancer types and inhibits growth and invasion by suppressing expression and activity of the epidermal growth factor receptor (EGFR) signaling pathway. While melanoma is not typically driven by EGFR signaling, expression of miR-7-5p is reduced in metastatic tumors compared to primary melanoma. Here, we investigated the biological and clinical significance of miR-7-5p in melanoma. Our results showed that augmenting miR-7-5p expression in vitro markedly reduced tumor cell viability, colony formation and induced cell cycle arrest. Furthermore, ectopic expression of miR-7-5p reduced migration and invasion of melanoma cells in vitro and reduced melanoma lung colonizationmetastasis in vivo. To investigate the mechanism underlying this effect, we used cDNA microarray analysis to identify a subset of putative miR-7-5p target genes associated with melanoma and metastasis. Of these, we confirmed nuclear factor kappa B (NF-κB) subunit RelA, as a novel direct target of miR-7-5p in melanoma cells, such that miR-7-5p suppresses NF-κB activity to decrease expression of canonical NF-κB target genes, including IL-1a, IL-6 and IL-8. Importantly, the effects of miR-7-5p on melanoma cell growth, cell cycle, migration and invasion were recapitulated by RelA knockdown. Finally, analysis of gene array datasets from multiple melanoma patient cohorts revealed an association between elevated RelA expression and poor survival, further emphasizing the clinical significance of RelA and its downstream signaling effectors.. Taken together, our data suggest that miR-7-5p replacement therapy might have clinical utility in melanoma to inhibit the metastatic process, in part through its inactivation of RelA/NF-kB signaling. Total RNA was extracted from WM266-4 cells transfected with miR-NC or miR-7-5p precursor molecules (30 nM) for 24 h, using Qiazol reagent (Qiagen).
2016-02-10 | E-GEOD-77196 | biostudies-arrayexpress
Project description:Cellular directed migration is critical to invasion-metastasis cascade of cancer cells. We used in vitro transwell model to screen two esophageal cancer cell lines (KYSE30/180) and obtained two pairs of subpopulations with distinc motiliyt ability. Then we used microarrays to detail the differentially expressed genes and microRNAs between these two cell sublines (30U/D and 180U/D) to identify those responsible for ESCC motility.
2015-12-31 | GSE67509 | GEO
Project description:Breast cancer (BC) is a commonly identified life-threatening type of cancer and a major cause of death among women worldwide. Several microRNAs (miRs), including miR-143-5p, have been reported to be vital for regulating hallmarks of cancer; however, the effect of miR-143-5p on BC requires further exploration. The present study performed bioinformatics analysis on GSE42072 and GSE41922 datasets from the National Center for Biotechnology Information Gene Expression Omnibus (GEO) database to identify miR-143-5p expression patterns. Furthermore, miR-143-5p expression was detected in BC cell lines and tissues via reverse transcription-quantitative PCR. Post-transfection with miR-143-5p mimics, Cell Counting Kit-8, colony formation and Transwell assays were performed to explore the effects of miR-143-5p on BC cell proliferation, colony formation, and migration. The association of miR-143-5p with the hypoxia-inducible factor-1α (HIF-1α)-associated glucose transporter 1 (GLUT1) pathway was explored via western blotting, immunofluorescence and dual-luciferase reporter assay. The present study detected high expression of miR-143-5p in BC tissue of the GSE42072 and serum of the GSE41922 datasets by GEO chip analysis. Additionally, the expression levels of miR-143-5p were decreased in BC tissues compared with those in adjacent healthy tissues, and low miR-143-5p expression was associated with a poorer prognosis and shorter survival time in patients with BC. In vitro, miR-143-5p expression levels were decreased in BC cells, and transfection with miR-143-5p mimics suppressed BC cell proliferation, colony formation, migration. Furthermore, miR-143-5p targeted the HIF-1α-related GLUT1 pathway, and inhibited HIF-1α and GLUT1 expression. Additionally, HIF-1α agonists reversed the miR-143-5p-induced inhibition during tumorigenesis. In conclusion, miR-143-5p exhibited low expression in BC tissues, and suppressed BC cell proliferation, colony formation, migration. Moreover, the antitumor effects of miR-143-5p targeted the HIF-1α-related GLUT1 pathway.
2022-02-26 | E-MTAB-11160 | biostudies-arrayexpress
Project description:Background: Androgen deprivation therapy (ADT) is the backbone of therapy for advanced prostate cancer (PCa). Despite the good initial response, castration resistance and metastatic progression will inevitably occur. Cancer-associated fibroblasts (CAFs) may be implicated in promoting metastasis of PCa after ADT. Our aim is to investigate the role and mechanism of CAF-derived exosomes involving in metastasis of PCa after ADT. Methods: PCa cells were co-cultured with exosomes derived from DHT-treated or ETOH-treated CAFs, and their migration and invasion differences under castration condition were examined both in vitro and in vivo. The miRNA profiles of exosomes derived from DHT-treated CAFs and matched ETOH-treated CAFs were analysed via next generation sequencing. The transfer of exosomal miR-146a-5p from CAFs to PCa cells was identified by fluorescent microscopy. The function and direct target gene of exosomal miR-146a-5p in PCa cells were confirmed through Transwell assays, luciferase reporter, and western blot. Findings: Compared with DHT-treated CAFs, exosomes derived from ETOH-treated CAFs dramatically increase migration and invasion of PCa cells under castration condition. MiR-146a-5p level in exosomes from ETOH-treated CAFs was significantly reduced. The loss of miR-146a-5p may strengthen the epithelial-mesenchymal transition (EMT) to accelerate cancer cells metastasis by modulating epidermal growth factor receptor (EGFR)/ERK pathway. Interpretation: CAFs-derived exosomal miR-146a-5p confers metastasis in PCa cells under ADT through the EGFR/ERK pathway and it may present a new treatment for PCa.
2022-08-02 | GSE154215 | GEO