Key Laboratory of Ruminant Molecular and Cellular Breeding, School of Agriculture, Ningxia University, 750021, Yinchuan, China.
NingXia Academy of Agriculture and Forestry Sciences, 750002, Yinchuan, China.
BMC Genomics. 2024 Apr 1;25(1):323. doi: 10.1186/s12864-024-10252-y.
Cow milk fat is an essential indicator for evaluating and measuring milk quality and cow performance. Growing research has identified the molecular functions of circular RNAs (circRNAs) necessary for mammary gland development and lactation in mammals.
The present study analyzed circRNA expression profiling data in mammary epithelial cells (MECs) from cows with highly variable milk fat percentage (MFP) using differential expression analysis and weighted gene co-expression network analysis (WGCNA).
A total of 309 differentially expressed circRNAs (DE-circRNAs) were identified in the high and low MFP groups. WGCNA analysis revealed that the pink module was significantly associated with MFP (r = - 0.85, P = 0.007). Parental genes of circRNAs in this module were enriched mainly in lipid metabolism-related signaling pathways, such as focal adhesion, ECM-receptor interaction, adherens junction and AMPK. Finally, six DE-circRNAs were screened from the pink module: circ_0010571, circ_0007797, circ_0002746, circ_0003052, circ_0004319, and circ_0012840. Among them, circ_0002746, circ_0003052, circ_0004319, and circ_0012840 had circular structures and were highly expressed in mammary tissues. Subcellular localization revealed that these four DE-circRNAs may play a regulatory role in the mammary glands of dairy cows, mainly as competitive endogenous RNAs (ceRNAs). Seven hub target genes (GNB1, GNG2, PLCB1, PLCG1, ATP6V0C, NDUFS4, and PIGH) were obtained by constructing the regulatory network of their ceRNAs and then analyzed by CytoHubba and MCODE plugins in Cytoscape. Functional enrichment analysis revealed that these genes are crucial and most probable ceRNA regulators in milk fat metabolism.
Our study identified several vital circRNAs and ceRNAs affecting milk fat synthesis, providing new research ideas and a theoretical basis for cow lactation, milk quality, and breed improvement.
牛奶脂肪是评估和衡量牛奶质量和奶牛性能的重要指标。越来越多的研究已经确定了在哺乳动物乳腺发育和泌乳过程中必需的环状 RNA（circRNA）的分子功能。
本研究通过差异表达分析和加权基因共表达网络分析（WGCNA），分析了具有高可变乳脂率（MFP）的奶牛乳腺上皮细胞（MEC）中的 circRNA 表达谱数据。
在高、低 MFP 组中，共鉴定出 309 个差异表达的 circRNA（DE-circRNA）。WGCNA 分析表明，粉色模块与 MFP 显著相关（r=-0.85，P=0.007）。该模块中 circRNA 的亲本基因主要富集在脂质代谢相关信号通路中，如焦点黏附、ECM-受体相互作用、黏着连接和 AMPK。最后，从粉色模块中筛选出 6 个 DE-circRNA：circ_0010571、circ_0007797、circ_0002746、circ_0003052、circ_0004319 和 circ_0012840。其中，circ_0002746、circ_0003052、circ_0004319 和 circ_0012840 具有环状结构，在乳腺组织中高表达。亚细胞定位显示，这 4 个 DE-circRNA 可能在奶牛乳腺中发挥调节作用，主要作为竞争性内源性 RNA（ceRNA）。通过构建 ceRNA 的调控网络，获得了 7 个关键靶基因（GNB1、GNG2、PLCB1、PLCG1、ATP6V0C、NDUFS4 和 PIGH），并通过 Cytoscape 中的 CytoHubba 和 MCODE 插件进行分析。功能富集分析表明，这些基因是乳脂肪代谢中关键且极有可能的 ceRNA 调控因子。
本研究鉴定了几个影响牛奶脂肪合成的重要 circRNA 和 ceRNA，为奶牛泌乳、牛奶质量和品种改良提供了新的研究思路和理论依据。
