CircRNA8220 Sponges MiR-8516 to Regulate Cell Viability and Milk Synthesis via Ras/MEK/ERK and PI3K/AKT/mTOR Pathways in Goat Mammary Epithelial Cells

Zhu, Chao; Zhu, Junru; He, Yizhu; Yin, Hao; Duan, Qiangde; Zhang, Lei; Cao, Binyun; An, Xiaopeng

doi:10.3390/ani10081347

Cited by 12 publications

(12 citation statements)

References 39 publications

(45 reference statements)

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“…The purpose of this research was to ascertain the signaling pathways that regulated cell proliferation and apoptosis through the FBXO18/circRNA211/miR-431/CSF1 axis. There was substantial evidence demonstrating that MAPK signaling pathway is involved in cell physiological activity [6,7,27,28]. In this study, overexpression circRNA211 or FBXO18 activated Ras proteins, which in turn triggered downstream phosphorylation levels of Raf, MEK, and ERK proteins.…”

Section: Discussionmentioning

confidence: 65%

“…CircRNAs may act as miRNA sponges to regulate the expression of miRNAs, which regulated the expression of target gene indirectly [3]. Although circRNAs have pleiotropic roles in a variety of biological processes including regulation of myoblasts differentiation in bovine [4], embryo implantation in mouse [5], and milk synthesis in goats [6,7], but their contribution to the formation of RE remains largely unclear.…”

Section: Introductionmentioning

confidence: 99%

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FBXO18/Circrna211/Mir-431/CSF1 Axis Regulates the Establishment of Endometrial Receptivity Though Activating MAPK and CSF1R/PI3K/AKT/Mtor Pathways in Dairy Goats

Yang

Liu

Zhang

et al. 2021

Preprint

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Background: Endometrial epithelial cells proliferation and secretion of various cytokines have a strong impact on the formation of receptive endometrium, which is known as a physiological status that allows an activated embryo to attach to the endometrium for a limited time. Circular RNAs and miRNAs can be involved in the dynamic physiological changes of endometrium by regulating relevant functional target genes in the uterus. Our work presented here with the ultimate purpose of revealing the latent molecular mechanism of FBXO18/circRNA211/miR-431/CSF1 axis in the establishment of endometrial receptivity of dairy goats.Results: In vitro, we found a regulatory network of FBXO18/circRNA211/miR-431/CSF1 in goat endometrial epithelial cells that circRNA211 severed as a sponge for miR-431, resulting in weakening the inhibition of miR-431 on target genes CSF1 and FBXO18. FBXO18/circRNA211/miR-431/CSF1 axis promoted the proliferation through regulating the key proteins of Ras, Raf, MEK, ERK in MAPK pathway via CCK-8, EdU, flow cytometry and Western blot assays. Furthermore, FBXO18/circRNA211/miR-431/CSF1 axis activated the phosphorylation of key proteins PI3K, AKT and mTOR in PI3K-mTOR pathway by CSF1R, thereby promoting the establishment of endometrial receptivity. In vivo models, mice injected with miR-431 agomir showed that the endometrial thickness and the number of pinopodes were significantly decreased by HE staining and scanning electron microscope. Immunohistochemistry results showed that VEGF and OPN proteins were down-regulated and MUC1 protein was up-regulated under the treatment of miR-431 agomir. Further study demonstrated that miR-431 inhibited embryo implantation by impeding the establishment of endometrial receptivity.Conclusion: Ultimately, our study revealed a regulatory mechanism of FBXO18/circRNA211/miR-431/CSF1 axis in goat endometrial epithelial cells. This circRNA/miRNA/mRNA regulatory network presented here in vitro and in vivo models may provide a novel insight into the potentially regulating endometrium biological functions and promoting the formation of endometrium receptivity.

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Section: Discussionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

FBXO18/Circrna211/Mir-431/CSF1 Axis Regulates the Establishment of Endometrial Receptivity Though Activating MAPK and CSF1R/PI3K/AKT/Mtor Pathways in Dairy Goats

Yang

Liu

Zhang

et al. 2021

Preprint

Self Cite

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“…Thus, a better understanding of the molecular mechanisms of mammary epithelial cell development is essential to obtain economic benefits. It has been observed that circRNAs can regulate proliferation and viability of goat mammary epithelial cells through their corresponding miRNAs ( Liu et al, 2020a ; Zhu et al, 2020 ). Analogous studies ( Liu et al, 2020b ) on the effect of circHIPK3 on the proliferation and differentiation of BMECs have been performed with cattle.…”

Section: Circular Rnasmentioning

confidence: 99%

“…Milk proteins were mentioned previously in the micRNA section, and corresponding studies have also been reported on circRNAs. For example, Zhu et al (2020) investigated the function and molecular mechanism of circRNA8220 in GMECs and found that there is a circRNA8220/miR-8516/STC2 pathway that promotes the synthesis of ß-casein. Liu et al (2020a) conducted similar studies that suggested that circ016910 acts as a sponge for miR-574-5p and reduces ß-casein secretion by GMECs.…”

Section: Circular Rnasmentioning

confidence: 99%

Progress on the Regulation of Ruminant Milk Fat by Noncoding RNAs and ceRNAs

Chen

et al. 2021

Front. Genet.

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Milk fat is not only a key factor affecting the quality of fresh milk but also a major target trait forbreeding. The regulation of milk fat involves multiple genes, network regulation and signal transduction. To explore recent discoveries of pathway regulation, we reviewed the published literature with a focus on functional noncoding RNAs and epigenetic regulation in ruminants. Results indicate that miRNAs play key roles in the regulation of milk fat synthesis and catabolism in ruminants. Although few data are available, merging evidence indicates that lncRNAs and circRNAs act on milk fat related genes through indirect action with microRNAs or RNAs in the ceRNA network to elicit positive effects on transcription. Although precise regulatory mechanisms remain unclear, most studies have focused on the regulation of the function of target genes through functional noncoding RNAs. Data to help identify factors that can regulate their own expression and function or to determine whether self-regulation involves positive and/or negative feedback are needed. Despite the growing body of research on the role of functional noncoding RNA in the control of ruminant milk fat, most data are still not translatable for field applications. Overall, the understanding of mechanisms whereby miRNA, lncRNA, circRNA, and ceRNA regulate ruminant milk fat remains an exciting area of research.

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“…On the one hand, some studies have shown that cir-cRNAs play an important role in regulating the lactation of livestock [3][4][5]. Some studies detected a total of 37,818 circRNAs in goat breast tissue, of which 864 circRNAs were differentially expressed, 611 were upregulated, and 253 were down-regulated [6], so they speculated that these circRNAs may be related to breast development and lactation.…”

Section: Introductionmentioning

confidence: 99%

Functional Role of circRNAs in the Regulation of Fetal Development, Muscle Development, and Lactation in Livestock

Chen

Tian

et al. 2021

BioMed Research International

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circRNAs are a class of endogenous noncoding RNA molecules with closed loop structures. They are mainly responsible for regulating gene expression in eukaryotic cells. With the emergence of high-throughput RNA sequencing (RNA-Seq) and new types of bioinformatics tools, thousands of circRNAs have been discovered, making circRNA one of the research hotspots. Recent studies have shown that circRNAs play an important regulatory role in the growth, reproduction, and formation of livestock products. They can not only regulate mammalian fetal growth and development but also have important regulatory effects on livestock muscle development and lactation. In this review, we briefly introduce the putative biogenic pathways and regulatory functions of circRNA and highlight our understanding of circRNA and its latest advances in fetal development, muscle development, and lactation biogenesis as well as expression in livestock. This review will provide a theoretical basis for the research and development of related industries.

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CircRNA8220 Sponges MiR-8516 to Regulate Cell Viability and Milk Synthesis via Ras/MEK/ERK and PI3K/AKT/mTOR Pathways in Goat Mammary Epithelial Cells

Cited by 12 publications

References 39 publications

FBXO18/Circrna211/Mir-431/CSF1 Axis Regulates the Establishment of Endometrial Receptivity Though Activating MAPK and CSF1R/PI3K/AKT/Mtor Pathways in Dairy Goats

FBXO18/Circrna211/Mir-431/CSF1 Axis Regulates the Establishment of Endometrial Receptivity Though Activating MAPK and CSF1R/PI3K/AKT/Mtor Pathways in Dairy Goats

Progress on the Regulation of Ruminant Milk Fat by Noncoding RNAs and ceRNAs

Functional Role of circRNAs in the Regulation of Fetal Development, Muscle Development, and Lactation in Livestock

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