Effect of immunosuppression in miRNAs from extracellular vesicles of colorectal cancer and their influence on the pre-metastatic niche

Scientific Reports
Valeria TubitaIgnacio Revuelta

Abstract

Colorectal cancer (CRC) occurs with more aggressiveness in kidney transplant recipients compared to the general population. Immunosuppressive therapy plays a crucial role in the development of post-transplant malignancy. Concretely, cyclosporine A (CsA) has intrinsic pro-oncologic properties, while several studies report a regression of cancer after the introduction of rapamycin (RAPA). However, their effect on the extracellular vesicle (EV) content from CRC cell lines and their relevance in the pre-metastatic niche have not yet been studied. Here, we investigated the effect of RAPA and CsA in EV-miRNAs from metastatic and non-metastatic CRC cell lines and the role of relevant miRNAs transferred into a pre-metastatic niche model. EV-miRNA profiles showed a significant upregulation of miR-6127, miR-6746-5p, and miR-6787-5p under RAPA treatment compared to CsA and untreated conditions in metastatic cell lines that were not observed in non-metastatic cells. From gene expression analysis of transfected lung fibroblasts, we identified 22 shared downregulated genes mostly represented by the histone family involved in chromatin organization, DNA packaging, and cell cycle. These results suggest that EV-miR-6127, miR-6746-5p and miR-678...Continue Reading

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Citations

Dec 22, 2019·International Journal of Molecular Sciences·Francesco MannavolaMarco Tucci
May 23, 2020·Scientific Reports·Joana Maria Ramis

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Datasets Mentioned

BETA
GSE123710

Methods Mentioned

BETA
Flow Cytometry
chips
transfections
transfection
Assay
chip

Software Mentioned

Target Scan
GraphPad
TargetScan
GraphPadPrism
Expression Console
FlowJo
Bioconductor
Tree Star
limma
NTA

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