Alterations in Serum MicroRNA Profile During Hemodialysis - Potential Biological Implications.

BACKGROUND/AIMS: Hemodialysis implies significant alterations in the profile of serum components. microRNAs (miRNAs) are present in the human serum and are considered to target distant tissues where they can regulate gene expression, thus affecting homeostasis. Whether hemodialysis alters the profile of miRNAs in the serum is not known.

METHODS

miRNA profiling in serum samples collected before and after hemodialysis was performed using miRNA qPCR arrays. The results were subsequently validated in an independent group of 10 hemodialyzed men. miRWalk database was used to identify mRNAs targeted by the miRNAs the levels of which changed after hemodialysis. The list of mRNAs was analyzed using the DAVID and PANTHER classification systems to identify pathways controlled by these miRNAs.

RESULTS

miRNA profiling showed that the levels of the majority of circulating miRNAs were increased at least two-fold (115 out of 179 tested) while the levels of only five miRNAs were found at least two-fold lower after hemodialysis. Validation study confirmed the majority of the array results. Bioinformatics analysis of validated and significantly upregulated miRNAs revealed that gonadotropin-releasing hormone receptor, cell cycle and cell pluripotency-related pathways were targeted.

CONCLUSION

Hemodialysis alters serum miRNA expression profile and this alteration may result in disruption of pathways contributing to subfertility and increased risk for cancer development being pathologies associated with hemodialysis.