Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jun 8;27(12):3682.
doi: 10.3390/molecules27123682.

The Expression and Bioinformatics Analysis of Circular RNAs in Endometritis Mouse Uterus Tissues

Zhiqiang Li  1   2   3 , Liying Shi  1   2   3 , Qianqing Li  1   2   3 , Jing Zhao  1   2   3 , Wenfa Lu  1   2   3 , Jun Wang  1   2   3
Affiliations

The Expression and Bioinformatics Analysis of Circular RNAs in Endometritis Mouse Uterus Tissues

Zhiqiang Li et al. Molecules. .

Abstract

Previous studies have shown that circular RNAs are directly or indirectly involved in the occurrence of various diseases by regulating gene expression. However, the acting mechanism of circular RNAs in endometritis remains unclear. In this study, we successfully established an endometritis model in mouse using Escherichia coli; endometrial integrity was destroyed, inflammatory cells infiltrated and the expression of IL-6, IL-1β, TNF-α was significantly up-regulated. We analyzed and screened the circular RNA expression profiles between healthy and endometritis-stricken mice by the Illumina HiSeq platform, and used qRT-PCR method to verify the different expressions of circular RNAs. Gene ontology (GO) analysis showed that circular RNAs were mainly involved in biological processes such as the positive regulation of transcription from RNA polymerase POL II promoter and the negative regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of circular RNAs target genes may be involved in the TGF-β signaling pathway. We verified the expression of TGF-β and its related factors; the mRNA of TGF-β1 and smad7 were significantly up-regulated in endometritis mouse (p < 0.01) and the protein expression level of p-smad3 was significantly decreased (p < 0.01). Finally, we constructed a circular RNAs−miRNA network to elucidate the potential regulatory relationship between two small molecules. This research may provide new ideas for circular RNAs in the treatment of endometritis.

Keywords: Escherichia coli; circular RNAs; endometritis; mouse.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Infusion of Escherichia coli to establish a mouse model of endometritis. (A,B), Effects of different concentrations of Escherichia coli on mRNA and protein expression of IL-6, IL-1β and TNFα. **, p < 0.01, ***, p < 0.001, indicates a significant difference compared with the control group. Section of uterine tissue from healthy (C) and endometritis (D) mice.
Figure 2
Figure 2
Effects of Escherichia coli on NF-κB. **, p < 0.01, indicating a significant difference compared with the NC group.
Figure 3
Figure 3
Main classifications of circular RNAs. Circular RNAs are mainly derived from exons, and the remaining sources are intergenic and introns.
Figure 4
Figure 4
Differentially expressed circular RNAs in healthy and endometritis mouse. Blue means down-regulation, red means up-regulation, grey means not significant.
Figure 5
Figure 5
qRT-PCR to verify the expression of five circular RNAs. **, p < 0.01, indicating a significant difference compared with the control group.
Figure 6
Figure 6
GO and KEGG pathway analysis of circular RNAs in healthy and endometritis mice. (A) GO analysis of the main biological roles of circular RNAs. (B) KEGG analysis of signaling pathways involved in circular RNAs.
Figure 7
Figure 7
Effects of Escherichia coli on TGFβ signaling pathway. (A) Effect of Escherichia coli on the mRNA expression of TGFβ, smad3, smad7. (B) Effects of Escherichia coli on the protein expression of smad3 and smad7. *, p < 0.05, **, p < 0.01, indicating a significant or extremely significant difference compared with the control group.
Figure 8
Figure 8
Construction of circular RNAs–miRNA network. Blue indicates down-regulated circular RNAs, red indicates up-regulated circular RNAs, linked to them are their targeted miRNAs.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Piersanti R.L., Zimpel R., Molinari P.C.C., Dickson M.J., Ma Z., Jeong K.C., Santos J.E.P., Sheldon I.M., Bromfield J.J. A model of clinical endometritis in Holstein heifers using pathogenic Escherichia coli and Trueperella pyogenes. J. Dairy. Sci. 2019;102:2686–2697. doi: 10.3168/jds.2018-15595. - DOI - PMC - PubMed
    1. Li W., Fu K., Lv X., Wang Y., Wang J., Li H., Tian W., Cao R. Lactoferrin suppresses lipopolysaccharide-induced endometritis in mice via down-regulation of the NF-κB pathway. Int. Immunopharmacol. 2015;28:695–699. doi: 10.1016/j.intimp.2015.07.040. - DOI - PubMed
    1. Patop I.L., Wüst S., Kadener S. Past, present, and future of circRNAs. EMBO J. 2019;38:e100836. doi: 10.15252/embj.2018100836. - DOI - PMC - PubMed
    1. Li Y., Zheng Q., Bao C., Li S., Guo W., Zhao J., Chen D., Gu J., He X., Huang S. Circular RNA is enriched and stable in exosomes: A promising biomarker for cancer diagnosis. Cell Res. 2015;25:981–984. doi: 10.1038/cr.2015.82. - DOI - PMC - PubMed
    1. Hansen T.B., Wiklund E.D., Bramsen J.B., Villadsen S.B., Statham A.L., Clark S.J., Kjems J. MiRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. EMBO J. 2011;30:4414–4422. doi: 10.1038/emboj.2011.359. - DOI - PMC - PubMed

LinkOut - more resources