MicroRNA expression in liver of whitefish (Coregonus lavaretus) exposed to microcystin-LR

Abstract

MicroRNAs (miRNAs) are small, highly conserved, non-coding RNAs that regulate gene expression of target mRNAs through cleavage or translational inhibition. In the field of toxicology, the relationship between toxicity and microRNA expression is poorly understood. In the present study we analyzed the abundance of 9 selected miRNAs (omy-miR-21, omy-miR-21t, omy-miR-122, omy-miR-125a, omy-miR-125b, omy-miR-125t, omy-miR-199-5a, omy-miR-295, omy-let-7a) and mRNA of 3 genes (histone H2A, ribosome protein rpl19, and Dicer which is a miRNA processing enzyme) in liver samples of whitefish exposed to Microcystin-LR (MC-LR) at a dose of 100µg*kg-1body weight for 24 or 48h. In the examined liver tissue, omymiR-122 showed the highest relative constitutive level, what is consistent with data obtained from fish and mammals. Unexpectedly, the reference H2A mRNA level was consistently up-regulated (over 20-fold; P<0.05) in fish liver after both 24 and 48h of exposure to MC-LR. The result may suggest that MC-LR acts as an initiator of specific cell-physiologic signals triggering DNA replication in fish liver cells. MC-LR treatment had no effect on the examined miRNAs levels, except for omy-miR-125a and omy-let-7a. Whereas omy-miR-125a was up-regulated (ER=2.68; S.E. 1.61-6.78; P<0.05), omy-let-7a was down-regulated (ER=0.55; S.E. 0.32-0.79; P<0.05) in whitefish liver after 48h of the treatment with MC-LR, when compared to controls. More work with the fish is essential for understanding the crosstalk of the regulatory network controlled by the two miRNAs in the context of MC-LR toxicity