Abstract
MicroRNAs (miRNAs) present in tissues and biofluids are emerging as sensitive and specific safety biomarkers. MiRNAs have not been thoroughly described in M. fascicularis, an animal model used in pharmaceutical industry especially in drug safety evaluation. Here we investigated the miRNAs in M. fascicularis. For Macaca mulatta, a closely related species of M. fascicularis, 619 stem-loop precursor miRNAs (pre-miRNAs) and 914 mature miRNAs are available in miRBase version 21. Using M. mulatta miRNAs as a reference list and homology search tools, we identified 604 pre-miRNAs and 913 mature miRNAs in the genome of M. fascicularis. In order to validate the miRNAs identified by homology search we attempted to sequence miRNAs expressed in kidney cortex from M. fascicularis. MiRNAs expressed in kidney cortex may indeed be released in urine upon kidney cortex damage and be potentially used to monitor drug induced kidney injury. Hence small RNA sequencing libraries were prepared using kidney cortex tissues obtained from three naive M. fascicularis and sequenced. Analysis of sequencing data indicated that 432 out of 913 mature miRNAs were expressed in kidney cortex tissues. Assigning these 432 miRNAs to pre-miRNAs revealed that 273 were expressed from both the -5p and -3p arms of 150 pre-miRNAs and 159 miRNAs expressed from either the -5p or -3p arm of 176 pre-miRNAs. Mapping sequencing reads to pre-miRNAs also facilitated the detection of twenty-two new miRNAs. To substantiate miRNAs identified by small RNA sequencing, 313 miRNAs were examined by RT-qPCR. Expression of 262 miRNAs in kidney cortex tissues ware confirmed by TaqMan microRNA RT-qPCR assays. Analysis of kidney cortex miRNA targeted genes suggested that they play important role in kidney development and function. Data presented in this study may serve as a valuable resource to assess the renal safety biomarker potential of miRNAs in Cynomolgus monkeys.
Highlights
MicroRNAs are a class of small (18–24 nucleotide long) RNAs that are involved in regulation of gene expression by targeting messenger RNAs
We investigated the miRNAs in M. fascicularis genome by homology search and attempted to validate miRNAs by small RNA sequencing and RT-qPCR using kidney cortex tissues
When compared to the human genome, M. fascicularis shares a higher degree of sequence homology with M. mulatta (99.2% versus 92.8%)
Summary
MicroRNAs (miRNAs) are a class of small (18–24 nucleotide long) RNAs that are involved in regulation of gene expression by targeting messenger RNAs (mRNA). MiRNAs present in biofluids are packed in exosomes or associated to proteins or lipoproteins and protected from enzymatic degradation. Because of their stability and specificity, several studies demonstrated the utility of circulating miRNAs as diagnostic and prognostic biomarkers in disease such as cancer, cardiac disease and autoimmune disease [8,9 and 10]. MiRNAs received much attention as global intracellular and intercellular regulators and as therapeutic targets and disease or safety biomarkers [11]. There is great interest in miRNA identification and profiling
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