Abstract
Milk casein and triglyceride content are important production traits in goats. Studies on mechanisms in milk casein secretion and mammary gland development is essential for milk goat breeding. miRNAs play an important role in goat lactation. While novel-miR-3880 is highly expressed at goat peak lactation stage, its molecular mechanism has not been studied. The purpose of the present study was to explore the relationship between novel-miR-3880 and lactation, as well as to construct a network among novel-miR-3880, ciRNA13761, and E74 like ETS transcription factor 2 (ELF2), thus further exploring their potential roles in milk components and mammary gland development. ELF2 was previously proven to be important in cell survival and proliferation, and 3′-UTR of ELF2 was predicted to have binding sites of novel-miR-3880. Our study found that the overexpression of novel-miR-3880 exerted anti-apoptotic and proliferative roles in GMEC, induced a boost in triglyceride synthesis, and caused a decrease in α s1-, α s2-, and β-casein, but an increase in κ-casein secretion. Furthermore, treatment in mice indicated that novel-miR-3880 could promote mammary gland development and extend the lactation period, while novel-miR-3880 expression was found to be suppressed by ciRNA13761 as a miRNA sponge. The present study explores a mechanism of triglyceride synthesis and casein secretion, and reveals a crosstalk between ciRNA13761/novel-miR-3880/ELF2 axis and PI3K/AKT/mTOR/S6K1 pathway, to gain a better understanding of lactation traits in dairy goats.
Highlights
Goat’s milk is regarded as a hypoallergenic milk type with therapeutic functions and is accepted as a major functional food (Roncada et al, 2002) when casein, including κ, β, αs1, and αs2-casein, is the main protein in goat’s milk (Singh and Singh, 1980; Chatchatee et al, 2001)
The results show that MEC proliferation would be suppressed when PI3K, AKT, mTOR, or S6K1 were inhibited (Supplementary Files S8a,b), but the participation of novel-miR-3880 and siELF2 played a positive part in freeing MEC to proliferate (Supplementary Files S8a,c–g)
The present study reveals that novelmiR-3880 targeted ELF2 and was sponged by ciRNA13761
Summary
Goat’s milk is regarded as a hypoallergenic milk type with therapeutic functions and is accepted as a major functional food (Roncada et al, 2002) when casein, including κ-, β-, αs1,- and αs2-casein, is the main protein in goat’s milk (Singh and Singh, 1980; Chatchatee et al, 2001). MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs of approximately 23 nt in length. They are reported to regulate gene expression by repressing translation or facilitating mRNA degradation (Ambros, 2004) and play an important role in goat lactation (Ji et al, 2017). Novel-miR-3880 was highly expressed during goat peak lactation period based on our previous sequencing data (Hou et al, 2017). The novel-miR-3880 expression data was selected from Supplementary File S1 (Hou et al, 2017). Our study explored effects of novel-miR-3880-related molecules on mammary
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