Different Expression Patterns of Exosomal miRNAs under Cyclosporin A and Rapamycin Treatment in Distinct Aggressiveness Colorectal Carcinomas

V. Tubita,¹ M. Ramírez-Bajo,¹ J. Lozano,² D. Moya-Rull,¹ J. Rovira,³ J. Campistol,^4,5,6 F. Diekmann,^1,4,5,6 I. Revuelta.^1,4,5,6

¹Experimental Laboratory of Nefrology and Kidney Transplant (LENIT). Biomedical Research Clinic Foundation (FCRB), Barcelona, Spain
²Bioinformatics Platform, CIBEREHD, Barcelona, Spain
³Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
⁴Renal Transplant Unit. Department of Nephrology and Kidney Transplant. Hospital Clinic, Barcelona, Spain
⁵REDinREN, Madrid, Spain
⁶Barcelona University, Barcelona, Spain.

Meeting: 2018 American Transplant Congress

Abstract number: A47

Keywords: Genomic markers, Post-transplant malignancy, Proliferation

Session Information

Session Name: Poster Session A: Biomarkers, Immune Monitoring and Outcomes

Session Type: Poster Session

Date: Saturday, June 2, 2018

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Hall 4EF

The aggressiveness of colorectal cancer (CRC) in kidney transplantation is much more significant than the increase in its incidence compared with the general population. The molecular mechanism of the different immnosuppressive drugs with antagonistic antineoplasic properties is not well characterized. Exosomes (Ex) are nanovesicles involved in tumor microenvironment by regulating immunity, angiogenesis and metastasis. Exosomal miRNAs are able of affect expression of a variety of target genes. Our aim is to investigate if colon cancer cells with different metastatic profiles treated with Cyclosporin A (CsA) and Rapamycin (RAPA) can induce the production of different Ex content that could explain the cancer progression in kidney transplant patients.

Metastatic (HCT116) and non metastatic (SW480) colorectal cell lines were treated with CsA (10 [micro]M) and RAPA (20nM). Ex isolation was made by ultracentrifugation, and Ex characterization by nanoparticle tracking analysis, flow cytometry, and electron microscopy. A comparative miRNAs profile by Affymetrix miRNA 4.1 Array Strips was made in miRNAs isolated from Ex released from conditioned cells under CsA and RAPA.

Bioinformatics analysis indicated that miR6787-5p, miR6746-5p, miR6127 were common and highly differentially expressed in Ex from HCT116 after treatments with both drugs. CsA downregulated and RAPA upregulated these three miRNAs in Ex from HCT116. However, these results were not shown in SW480-Ex. We identified putative target genes related to the miRNAs implicated in the NOTCH signaling, and in immunoregulatory/inflammatory processes.

In conclusion, CsA and RAPA induce a different exosomal miRNAs expression pattern in metastatic cancer cell line, not evidenced in non-metastatic cells. Exosomal miRNAs could be a potential biomarker in cancer progression and metastasis.

CITATION INFORMATION: Tubita V., Ramírez-Bajo M., Lozano J., Moya-Rull D., Rovira J., Campistol J., Diekmann F., Revuelta I. Different Expression Patterns of Exosomal miRNAs under Cyclosporin A and Rapamycin Treatment in Distinct Aggressiveness Colorectal Carcinomas Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Tubita V, Ramírez-Bajo M, Lozano J, Moya-Rull D, Rovira J, Campistol J, Diekmann F, Revuelta^{1 6}I. Different Expression Patterns of Exosomal miRNAs under Cyclosporin A and Rapamycin Treatment in Distinct Aggressiveness Colorectal Carcinomas [abstract]. https://atcmeetingabstracts.com/abstract/different-expression-patterns-of-exosomal-mirnas-under-cyclosporin-a-and-rapamycin-treatment-in-distinct-aggressiveness-colorectal-carcinomas/. Accessed November 21, 2024.

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