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Potential regulatory role of microRNAs in the development of bovine gastrointestinal tract during early life

ABSTRACT: Purpose: The aims of this study were to profile miRNAs throughout the GIT during the early life of dairy calves and to investigate their potential regulatory roles in the development of bovine GIT. Results: The expression of miR-143 was abundant in all three gut regions and under all the time points and it targets genes involved primarily in the proliferation of connective tissue cells and muscle cells, suggesting its association with rapid tissue development during the early life of calves. The expression of miR-10, miR-146, miR-191, miR-33, miR-7, miR-96, miR-99/100, miR-486, miR-145, and miR-211 displayed significant temporal differences (FDR < 0.05), while miR-192/215, miR-194, miR-196,miR-205 and miR-31 revealed significant regional differences (FDR<0.05) throughout the GIT. Expression levels of miR-15/16, miR-29 and miR-196 were positively correlated with copy numbers of 16S rRNA gene of Bifidobacterium or Lactobacillus species or both of them (P < 0.05). Functional analysis using Ingenuity Pathway Analysis identified above mentioned differentially expressed miRNAs as potential regulators of gut tissue cells proliferation and differentiation, and bacterial density-associated miRNAs as modulators of development of lymphoid tissues (miR-196), maturation of dendritic cells (miR-29) and development of immune cells (miR-15/16). Conclusion: This present study revealed temporal and regional changes in miRNA expression, correlation between miRNA expression and microbial population during early life suggest their potential roles in host-microbial interactions during the gut development.

ORGANISM(S): Bos taurus

PROVIDER: GSE52193 | GEO | 2016/10/29

SECONDARY ACCESSION(S): PRJNA227138

REPOSITORIES: GEO

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Project description:We tested the hypothesis that a panel of placental mammal-specific miRNAs and their targets play important to establish receptivity to implantation and their dysregulated expression may be a feature in women with early pregnancy loss. Relative expression levels of miR-340-5p, −542-3p, and −671-5p all increased following treatment of Ishikawa cells with progesterone (10 μg/ml) for 24 hrs (p < 0.05). RNA sequencing of these P4-treated cells identified co-ordinate changes to 6,367 transcripts of which 1713 were predicted targets of miR-340-5p, 670 of miR-542-3p, and 618 of miR-671-5p. Quantitative proteomic analysis of Ishikawa cells transfected with mimic or inhibitor (48 hrs: n=3 biological replicates) for each of the P4-regulated miRNAs was carried out to identify targets of these miRNAs. Excluding off target effects, mir-340-5p mimic altered 1,369 proteins while inhibition changed expression of 376 proteins (p < 0.05) of which, 72 were common to both treatments. A total of 280 proteins were identified between predicted (mirDB) and confirmed (in vitro) targets. In total, 171 proteins predicted to be targets by mirDB were altered in vitro by treatment with miR-340-5p mimic or inhibitor and were also altered by treatment of endometrial epithelial cells with P4. In vitro targets of miR-542-3p identified 1,378 proteins altered by mimic while inhibition altered 975 a core of 200 proteins were changed by both. 100 protein targets were predicted and only 46 proteins were P4 regulated. miR-671-mimic altered 1,252 proteins with inhibition changing 492 proteins of which 97 were common to both, 95 were miDB predicted targets and 46 were also P4-regulated. All miRNAs were detected in endometrial biopsies taken from patients during the luteal phase of their cycle, irrespective of prior or future pregnancy outcomes Expression of mir-340-5p showed an overall increase in patients who had previously suffered a miscarriage and had a subsequent miscarriage, as compared to those who had infertility or previous miscarriage and subsequently went on to have a life birth outcome. The regulation of these miRNAs and their protein targets regulate the function of transport and secretion, and adhesion of the endometrial epithelia required for successful implantation in humans. Dysfunction of these miRNAs (and therefore the targets they regulate) may contribute to endometrial-derived recurrent pregnancy loss in women.

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Potential regulatory role of microRNAs in the development of bovine gastrointestinal tract during early life

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