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Regulation of hepatic microRNAs in response to early stage Echinococcus multilocularis egg enfection in C57BL/6 mice

ABSTRACT: Regulation of hepatic microRNAs in response to early stage Echinococcus multilocularis egg enfection in C57BL/6 mice

PROVIDER: PRJNA609662 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11213892.fastq.gz	Fastqsanger.gz
	SRR11213893.fastq.gz	Fastqsanger.gz
	SRR11213894.fastq.gz	Fastqsanger.gz
	SRR11213895.fastq.gz	Fastqsanger.gz
	SRR11213896.fastq.gz	Fastqsanger.gz

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Project description:The cestodes Echinococcus granulosus and Echinococcus multilocularis, as the pathogens of cystic echinococcosis and alveolar echinococcosis respectively, can cause significant health problems to the host and considerable socio-economic losses as a consequence. Based on the genomic data regarding these two species available in public database recently, we carried out high-throughput mRNA and small RNA transcriptomic sequencing of them and generate enormous transcriptomic datasets. A total of 34,717,856 reads (79.79%) mapped to E. granulosus genome, and 38,882,179 reads (87.61%) mapped to E. multiloculari genome. A total of 24,550 (7,925 known and 16,625 novel transcripts) and 23,771 transcripts (8,432 known and 15,339 novel transcripts) were assembled for E. granulosus and E. multilocularis respectively, and the assembly yielded 11,330 genes (6,815 known and 4,515 novel genes) for E. granulosus and 10,101 genes (7,051 known and 3,050 novel genes) for E. multilocularis, compared with the reference genome data. Bioinformatic analysis identified 6,826 AS events from 3,774 E. granulosus genes (33.31%) and 6,644 AS events in 3,611 E. multilocularis genes (35.75%). A total of 76,674 distinct microRNAs of E. granulosus and 115,742 of E. multilocularis were also obtained from small RNA transcriptome sequencing reads. Of these, there were 20 microRNAs of E. granulosus and 22 microRNAs of E. multilocularis that belonged to 19 and 21 microRNA families common to other metazoan lineages separately. 76 and 90 novel microRNAs so far unique to E. granulosus and E. multilocularis were also identified respectively. This study represents an extensive mRNA and small RNA transcriptome dataset obtained from the deep sequencing of these two cestode species. The findings will facilitate a more fundamental understanding of cestode biology, evolution, the host-parasite interplay, and provide new insights into the pathophysiology of echinococcosis, contributing to the development of improved interventions for disease control.

Project description:We present a comprehensive analysis of the hepatic miRNA transcriptome at one month post-infection of experimental primary alveolar echinococcosis (AE), a parasitic infection caused upon ingestion of E. multilocularis eggs. Liver tissues were collected from infected and non-infected C57BL/6 mice, then small RNA libraries were prepared for next-generation sequencing (NGS). We conducted a Stem-loop RT-qPCR for validation of most dysregulated miRNAs. In infected mice, the expression levels of 28 miRNAs were significantly altered. Of these, 9 were up-regulated (fold change (FC) ≥ 1.5) and 19 were down-regulated (FC ≤ 0.66) as compared to the non-infected controls. In infected livers, mmu-miR-148a-3p and mmu-miR-101b-3p were 8- and 6-fold down-regulated, respectively, and the expression of mmu-miR-22-3p was reduced by 50%, compared to non-infected liver tissue. Conversely, significantly higher hepatic levels were noted for Mus musculus (mmu)-miR-21a-5p (FC = 2.3) and mmu-miR-122-5p (FC = 1.8). In addition, the relative mRNA expression levels of five genes (vegfa, mtor, hif1-α, fasn and acsl1) that were identified as targets of down-regulated miRNAs were significantly enhanced. All the five genes exhibited a higher expression level in livers of E. multilocularis infected mice compared to non-infected mice. Finally, we studied the issue related to functionally mature arm selection preference (5p and/or 3p) from the miRNA precursor and showed that 9 pre-miRNAs exhibited different arm selection preferences in normal versus infected liver tissues. In conclusion, this study provides first evidence that miRNAs are regulated early in primary murine AE. Our findings raise intriguing questions such as (i) how E. multilocularis affects hepatic miRNA expression;(ii) what are the alterations in miRNA expression patterns in more advanced AE-stages; and (iii) which hepatic cellular, metabolic and/or immunologic processes are modulated through altered miRNAs in AE. Thus, further research on the regulation of miRNAs during AE is needed, since miRNAs constitute an attractive potential option for development of novel therapeutic approaches against AE.

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Regulation of hepatic microRNAs in response to early stage Echinococcus multilocularis egg enfection in C57BL/6 mice

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