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ROLE OF EXOSOMAL miRNAs IN METASTATIC POST-TRANSPLANT COLORECTAL CARCINOMA UNDER RAPAMYCIN AND CYCLOSPORINE (Clariom_S_Human)

ABSTRACT: Immunosuppression plays a crucial role in the development of cancer which remains a major cause of mortality in kidney transplant recipients. Cancer Exosomes (Exos) are extracellular vesicles described as modulators of tumor invasion and metastasis. This paper describes the effect of RAPA and CsA, two immunosuppressive drugs with different oncogenic proprieties, in Exos of colorectal cancer (CRC) cell lines. RAPA induces an increased Exos production and an overexpression of miR-6127, miR-6746-5p, and miR-6787-5p in Exos from a metastatic cell line. These miRNAs produce a significant down-regulation of epigenetic genes involved in cell cycle, chromatin and DNA regulation pre-metastatic niche. Our results describe a potential mechanism by RAPA in modulating pre-metastatic niche in post-transplant metastatic CRC through these exosomal miRNAs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE123709 | GEO | 2019/08/20

REPOSITORIES: GEO

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ROLE OF EXOSOMAL miRNAs IN METASTATIC POST-TRANSPLANT COLORECTAL CARCINOMA UNDER RAPAMYCIN AND CYCLOSPORINE (miRNA-4)

Project description:Immunosuppression plays a crucial role in the development of cancer which remains a major cause of mortality in kidney transplant recipients. Cancer Exosomes (Exos) are extracellular vesicles described as modulators of tumor invasion and metastasis. This paper describes the effect of RAPA and CsA, two immunosuppressive drugs with different oncogenic proprieties, in Exos of colorectal cancer (CRC) cell lines. RAPA induces an increased Exos production and an overexpression of miR-6127, miR-6746-5p, and miR-6787-5p in Exos from a metastatic cell line. These miRNAs produce a significant down-regulation of epigenetic genes involved in cell cycle, chromatin and DNA regulation pre-metastatic niche. Our results describe a potential mechanism by RAPA in modulating pre-metastatic niche in post-transplant metastatic CRC through these exosomal miRNAs.

2019-08-20 | GSE123708 | GEO

miRNA sequencing detecting miRNA cargo from PRP derived exosomes isolated from young donors and old donors

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2019-09-27 | PXD015369 | Pride

Colorectal Cancer-derived Small Extracellular Vesicles Create an Inflammatory Pre-metastatic Niche through Macrophage Polarization in Liver Metastasis

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Project description:Background: MicroRNA-196b-5p (miR-196b-5p) has been previously involved in carcinogenesis, though its role in colorectal cancer (CRC) patients and biology remains controversially. In our current study, we systematically explored the clinical significance and biological relevance of miR-196b-5p, as well as the underlying molecular mechanisms regulated by miR-196b-5p in colorectal cancer. Methods: In this study, we measured miR-196b-5p expression by quantitative RT-PCR and explored its prognostic value in two independent patient cohorts of 292 CRC patients. In a panel of CRC cell lines, using transient and stable gain and loss of function experiments, we evaluated the impact on in vitro proliferation, chemo-sensitivity and migration/invasion as well as in vivo metastases-formation. The molecular mode of action was characterized by mRNA transcriptome profiling, target prediction tools, luciferase-interaction assays, and pheno-copy gene knock-down experiments for potential target genes. Results: Our clinical data indicate that low levels of miR-196b-5p in CRC are significantly associated with metastatic disease and poor patient outcome in both independent cohorts (p<0.05). A loss of function of miR-196b-5p led to increased cancer cell migration/invasion and metastases formation, which can be partly explained by direct interaction with HOXB7 and GalNT5 mRNA, which both of them influence CRC cell migration. Conclusion: In conclusion, our data suggest that low levels of miR-196b-5p are associated with poor prognosis in CRC. MiR-196b-5p has an effect on CRC progression through genes important for cancer cell migration and metastases.

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