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Effect of immunosuppression in miRNAs from extracellular vesicles of colorectal cancer and their influence on the pre-metastatic niche
- Source :
- Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019), Scientific Reports, r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol, instname
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
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-6787-5p could be a potential epigenetic mechanism induced by RAPA therapy in the regulation of the pre-metastatic niche of post-transplant colorectal cancer.
- Subjects :
- 0301 basic medicine
Transcription, Genetic
Colorectal cancer
Population
lcsh:Medicine
Biology
Article
Epigenesis, Genetic
Extracellular Vesicles
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Cell Line, Tumor
microRNA
medicine
Humans
lcsh:Science
education
Immunosuppression Therapy
Sirolimus
education.field_of_study
Multidisciplinary
Gene Expression Profiling
lcsh:R
Extracellular vesicle
Cell cycle
medicine.disease
Chromatin
MicroRNAs
Mechanisms of disease
030104 developmental biology
Histone
Colonic Neoplasms
miRNAs
Cyclosporine
Cancer research
biology.protein
lcsh:Q
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....fd111f9f3ee32076312b0519120ac4dd