Exosome-delivered microRNAs of “chromosome 19 microRNA cluster” as immunomodulators in pregnancy and tumorigenesis

Jörn Bullerdiek,Inga Flor

doi:10.1186/1755-8166-5-27

Abstract

BackgroundStructural rearrangements of chromosomal band 19q13 are a non-random cytogenetic abnormality in thyroid adenomas and adenomatous goiters and lead to an expression of miRNAs of the chromosome 19 microRNA cluster C19MC. Normally, expression of these miRNAs is silenced except for embryonic stem cells and the placenta where they represent the majority of miRNAs not only in the trophoblast but also in exosomes derived from it.Presentation of the hypothesisWe have advanced the hypothesis that as part of the feto-maternal communication miRNAs of C19MC serve immunomodulatory functions in the placenta and confer a growth advantage to thyroid nodules by protecting them against autoimmune attacks. More precisely, the exosomes containing these miRNAs may specifically target immune cells in their local environment as well as systemically by transferring their cargo to recipient cells. Within these target cells the transferred miRNAs can interact with mRNAs of the recipient cells thereby suppressing their immune-specific functions.Testing the hypothesisExperiments used to demonstrate the immunomodulatory capacity of placenta-derived exosomes can be modified by transfecting the target cells with those miRNAs of C19MC represented in placental exosomes.Implications of the hypothesisMimics of C19MC-derived miRNAs might develop to useful drug candidates for the treatment of autoimmune disease as e.g. rheumatoid arthritis and Sjögren’s syndrome and for the prevention of transplant rejection. In case of tumor entities with elevated expression of C19MC miRNAs these miRNAs may be interesting targets for treatment with appropriate antagonists.

Highlights

Structural rearrangements of chromosomal band 19q13 are a non-random cytogenetic abnormality in thyroid adenomas and adenomatous goiters and lead to an expression of miRNAs of the chromosome 19 microRNA cluster C19MC
Testing the hypothesis: Experiments used to demonstrate the immunomodulatory capacity of placenta-derived exosomes can be modified by transfecting the target cells with those miRNAs of C19MC represented in placental exosomes
By applying molecular-cytogenetic methods on established cell lines it was possible to narrow down the breakpoints to a region of about 150 kbp [2] which was later shown to harbor C19MC, the largest human microRNA cluster at all [3] (Figure 1)

Summary

Introduction

Structural rearrangements of chromosomal band 19q13 are a non-random cytogenetic abnormality in thyroid adenomas and adenomatous goiters and lead to an expression of miRNAs of the chromosome 19 microRNA cluster C19MC. Testing the hypothesis: Experiments used to demonstrate the immunomodulatory capacity of placenta-derived exosomes can be modified by transfecting the target cells with those miRNAs of C19MC represented in placental exosomes. Implications of the hypothesis: Mimics of C19MC-derived miRNAs might develop to useful drug candidates for the treatment of autoimmune disease as e.g. rheumatoid arthritis and Sjögren’s syndrome and for the prevention of transplant rejection.

Results

Conclusion