An integrated analysis of mRNAs, lncRNAs, and miRNAs based on weighted gene co-expression network analysis involved in bovine endometritis

Abstract

In dairy cattle, endometritis is a severe infectious disease that occurs following parturition. It is clear that genetic factors are involved in the etiology of endometritis, however, the molecular pathogenesis of endometritis is not entirely understood. In this study, a system biology approach was used to better understand the molecular mechanisms underlying the development of endometritis. Forty transcriptomic datasets comprising of 20 RNA-Seq (GSE66825) and 20 miRNA-Seq (GSE66826) were obtained from the GEO database. Next, the co-expressed modules were constructed based on RNA-Seq (Rb-modules) and miRNA-Seq (mb-modules) data, separately, using a weighted gene co-expression network analysis (WGCNA) approach. Preservation analysis was used to find the non-preserved Rb-modules in endometritis samples. Afterward, the non-preserved Rb-modules were assigned to the mb-modules to construct the integrated regulatory networks. Just highly connected genes (hubs) in the networks were considered and functional enrichment analysis was used to identify the biological pathways associated with the development of the disease. Furthermore, additional bioinformatic analysis including protein–protein interactions network and miRNA target prediction were applied to enhance the reliability of the results. Thirty-five Rb-modules and 10 mb-modules were identified and 19 and 10 modules were non-preserved, respectively, which were enriched in biological pathways related to endometritis like inflammation and ciliogenesis. Two non-preserved Rb-modules were significantly assigned to three mb-modules and three and two important sub-networks in the Rb-modules were identified, respectively, including important mRNAs, lncRNAs and miRNAs genes like IRAK1, CASP3, CCDC40, CCDC39, ZMYND10, FOXJ1, TLR4, IL10, STAT3, FN1, AKT1, CD68, ENSBTAG00000049936, ENSBTAG00000050527, ENSBTAG00000051242, ENSBTAG00000049287, bta-miR-449, bta-miR-484, bta-miR-149, bta-miR-30b and bta-miR-423. The potential roles of these genes have been previously demonstrated in endometritis or related pathways, which reinforced putative functions of the suggested integrated regulatory networks in the endometritis pathogenesis. These findings may help further elucidate the underlying mechanisms of bovine endometritis.

miR-484: A Potential Biomarker in Health and Disease

“…Low-dose ionizing radiation exposure induces downregulation of miR-484 expression in small cell lung cancer cells ( 51 , 52 ). Chronic inflammation stimulates keratin-forming cells and endometrial cells to upregulate miR-484 ( 53 , 54 ).…”

In-depth systems biological evaluation of bovine alveolar macrophages suggests novel insights into molecular mechanisms underlying Mycobacterium bovis infection

“…In agreement with the main hypothesis of this study, M. bovis infection in bAMs was able to change the network characteristics of 67% of the identified modules (14 out of 21) compared to the non-infected control bAMs. Then, functional enrichment analysis based on the biological processes and KEGG pathways showed that among the 14 non-preserved modules, 7 non-preserved modules, including blue, brown, green, pink, salmon, tan, and turquoise were directly involved in host-pathogen interactions and could be important candidates for studying pathogenic mechanisms of bTB as in previous similar studies, these candidate non-preserved modules were successfully used as key modules to describe the complex etiology of several bovine diseases, such as bovine mastitis ( Bakhtiarizadeh et al, 2020 ), bovine respiratory disease (BRD; Hasankhani et al, 2021b ), bovine endometritis ( Sheybani et al, 2021 ), and Johne’s disease ( Heidari et al, 2021 ). It should be noted that loss of connection or alteration of the connectivity patterns and network density in the non-preserved modules can be attributed to the abnormal expression of several genes in M. bovis -infected conditions, which can be key factors in the development of bTB.…”

In Silico Identification of lncRNAs Regulating Sperm Motility in the Turkey (Meleagris gallopavo L.)

“…Mutations within the CCDC40 are associated with cilia and sperm dysmotility [ 72 ], and are suspected to be involved in idiopathic male infertility [ 64 ]. Moreover, co-expression and interactions between lncRNAs and the CCDC40 and ZMYND10 are involved in bovine endometritis [ 73 ]. These distant examples demonstrate that those genes are prone to the regulatory function of the lncRNAs.…”