miR-380-3p promotes β-casein expression by targeting α(S1)-casein in goat mammary epithelial cells

OBJECTIVE: α(S1)-Casein is more closely associated with milk allergic reaction than other milk protein components. microRNA (miRNA) is a class of small non-coding RNAs that modulate multiple biological progresses by the target gene. However, the post-transcriptional regulation of α(S1)-casein expression by miRNA in ruminants remains unclear. This study aims to explore the regulatory roles of miR-380-3p on α(S1)-casein synthesis in goat mammary epithelial cells (GMEC). METHODS: α(S1)-Casein gene and miR-380-3p expression was measured in dairy goat mammary gland by quantitative real-time polymerase chain reaction (qRT-PCR). miR-380-3p overexpression and knockdown were performed by miR-380-3p mimic or inhibitor in GMEC. The effect of miR-380-3p on αS1-casein synthesis was detected by qRT-PCR, western blot, luciferase and chromatin immunoprecipitation assays in GMEC. RESULTS: Compared with middle-lactation period, α(S1)-casein gene expression is increased, while miR-380-3p expression is decreased during peak-lactation of dairy goats. miR-380-3p reduces α(S1)-casein abundance by targeting the 3′-untranslated region (3′UTR) of α(S1)-casein mRNA in GMEC. miR-380-3p enhances β-casein expression and signal transducer and activator of transcription 5a (STAT5a) activity. Moreover, miR-380-3p promotes β-casein abundance through target gene α(S1)-casein, and activates β-casein transcription by enhancing the binding of STAT5 to β-casein gene promoter region. CONCLUSION: miR-380-3p decreases α(S1)-casein expression and increases β-casein expression by targeting α(S1)-casein in GMEC, which supplies a novel strategy for reducing milk allergic potential and building up milk quality in ruminants.