EXOSOME-DERIVED MICRORNAS IN BREAST, OVARIAN, LUNG AND MESOTHELIOMA MALIGNANT ASCITES FLUIDS

Natty Federman 1 Olga Vaksman 1 Yoav Smith 4 Ben Davidson 2,3 Reuven Reich 1
1Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem
2Division of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo
3The Medical Faculty, University of Oslo, Oslo
4Bioinformatics Units, The Hebrew University of Jerusalem, Jerusalem

Background:

Ascites fluids might accumulate in serosal cavities as a consequence of benign and malignant processes. It usually contains cells of various origins and fluid rich in proteins and cell-derived small particles. Exosomes, naturally occuring biological nanovesicles have been shown to contain lipids, proteins, and nucleic acid sequences including microRNAs. It has been implicated that this content might be considered as a “messenger system” that exhibits paracrine bioactivities and facilitate tumor communication within the local tumor microenvironment and distantly through transfer of regulatory messages to other cells.

Study aim:

Our aim is to examine the differentially expressed a-cellular microRNA profile in breast, ovarian, lung and mesothelioma derived ascites fluids.

Methods and materials:

Exosomal microRNAs from effusion fluids of breast, ovarian, lung carcinoma and mesothelioma patients were extracted and analyzed using TaqMan, low density microRNA array cards and bioinformatics tools to identify their predicted targets, the molecular networks they may affect and differences in microRNA expression from effusion fluid in these malignancies. Validation was performed using qPCR.

Results:

222 microRNAs were detected in exosomal fraction of which 12 were ovarian effusion specific and 9 were breast effusion specific. Using Onto-Tools suite, MAPK, Focal adhesion, mTOR and WNT pathways were affected in ovarian carcinoma while PI-PLC and Ras-Erk pathways in breast carcinoma. Likewise, mTOR pathway was affected in lung carcinoma while ErbB pathway in mesothelioma.

Significant differences in expression of microRNAs from effusion fluid in these malignancies were found such as miR21, miR23 and miR205.

Conclusions:

To our knowledge, this is the first study to evaluate the differential expression of exosomal microRNAs from effusion fluid in these malignancies. The potential activation of the various pathways indicates on significant difference between the exosomal signaling in these diseases.








 




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