ARID3A plays a key regulatory role in palmitic acid‐stimulated milk fat synthesis in mouse mammary epithelial cells

Guo, Xudong; Qi, Hao; Lin, Gang; Yu, Jiegen; Zhang, Minghui; Gao, Xuejun

doi:10.1002/cbin.12003

Cited by 5 publications

(3 citation statements)

References 36 publications

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“…9 As far as we know, a few reports have also shown that protein members in SWI/ SNF, a main chromatin remodeling complex, can respond to extracellular nutrient signals to regulate milk synthesis in MECs. For examples, ARID1B plays an inhibitory role in Met stimulation on mTOR transcriptional activation and milk synthesis in MECs 10 ; ARID3A mediates palmitic acid stimulation on mTOR mRNA expression and milk lipid synthesis in MECs 28 ; and BRM, as a positive regulator, participates in proliferation of MECs and mediates Leu induction on mTOR transcriptional activation and protein phosphorylation. 11 In this study, we further uncover that BRCC36 is a negative regulator of BRG1 protein level, mTOR mRNA level, and protein phosphorylation.…”

Section: ■ Discussionmentioning

confidence: 99%

Methionine Promotes Milk Synthesis through the BRCC36-BRG1-mTOR Signaling Axis in Mammary Epithelial Cells

Xie,

Li,

Zhang

et al. 2024

J. Agric. Food Chem.

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Methionine (Met) functions as a key stimulator on the mTOR signaling pathway and milk synthesis, but the molecular mechanism remains incompletely understood. We investigated the regulatory roles of BRCC36 in Met-stimulated milk lipid and protein synthesis, cell proliferation, and the mTOR signaling pathway. Knockdown of BRCC36 promoted milk lipid and protein synthesis in HC11 cells as well as cell proliferation by increasing the levels of mTOR gene transcription and protein phosphorylation. Conversely, the gene activation of BRCC36 had opposite effects. Furthermore, BRCC36 gene activation completely blocked Met stimulation on the BRG1 protein level and mTOR mRNA level and protein phosphorylation. BRCC36 bound to BRG1, and BRCC36 and BRG1 bound to the same region on the mTOR promoter. BRCC36 inhibited the BRG1 protein level and the binding of BRG1 to the mTOR promoter. Met decreased the BRCC36 protein level, and this effect was significantly attenuated by MG132 but not affected by cycloheximide or chloroquine. We further showed that Met increased BRCC36 ubiquitination degradation. Our findings reveal that Met promotes milk lipid and protein synthesis in MECs through the BRCC36-BRG1-mTOR signaling axis.

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Section: ■ Discussionmentioning

confidence: 99%

Methionine Promotes Milk Synthesis through the BRCC36-BRG1-mTOR Signaling Axis in Mammary Epithelial Cells

Xie,

Li,

Zhang

et al. 2024

J. Agric. Food Chem.

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“…It is yet unknown how GPR110 can stimulate mTOR phosphorylation and SREBP-1c expression. We have previously shown that PA can stimulate mTOR phosphorylation and SREBP-1c expression through activating PI3K (46,47) , which is often a downstream signalling molecular of many GPCR such as GPCR6A (8,47) . We thus speculate that GPR110 can stimulate mTOR phosphorylation through the PI3K signalling.…”

Section: Discussionmentioning

confidence: 99%

Comparative transcriptomic analysis of mammary gland tissues reveals the critical role of GPR110 in palmitic acid-stimulated milk protein and fat synthesis

Chen

et al. 2023

Br J Nutr

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The G protein coupled receptors (GPCRs) sensing nutritional signals (amino acids, fatty acids, glucose, etc.) are not fully understood. In this research, we used transcriptome-sequencing to analyze differentially expressed genes (DEGs) in mouse mammary gland tissues at puberty, lactation and involution stages, in which 8 GPCRs were selected out and verified by qRT-PCR assay. It was further identified the role of GPR110 mediating nutrients including palmitic acid (PA) and methionine (Met) to improve milk synthesis using mouse mammary epithelial cell line HC11. PA but not Met affected GPR110 expression in a dose-dependent manner. GPR110 knockdown decreased milk protein and fat synthesis and cell proliferation, and blocked the stimulation of PA on mTOR phosphorylation and SREBP-1c expression. In summary, these experimental results disclose DEGs related to lactation and reveal that GPR110 mediates PA to activate the mTOR and SREBP-1c pathways to promote milk protein and fat synthesis.

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“…Consolidating our target mRNA predictions from TargetScan and miRDB platforms established a list of 192 putative mmu-let-7b-5p mRNA targets showing increased abundance during infection, including Integrin Beta 3 subunit (Itgb3, Log2 FC = 2.35), Argonaute RISC Catalytic Component 2 (Ago2, Log2 FC = 1.37), Dual-specificity phosphatase 9 (Dusp9, Log2 FC = 1.94) (Figure2A) and 7 mRNAs encoding for transcription factors (TFs) or epigenetic regulators (ERs), i.e. Arid3a, E2f6, Hmga1, Klf8, Nr6a1, Pbx1, and Zfp202 (Figure2B), which are involved in regulation of proliferation regulation, cell differentiation, DNA structure modification, and cancer-related signaling pathways(Trimarchi et al 2001, Patterson et al 2008, Wang et al 2022, Guo et al 2023, Bai et al 2024, Kao et al 2024, Zhang et al 2024.…”

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MAPPING CHANGES OF MIRNA-MRNA NETWORKS INLEISHMANIA-INFECTEDMACROPHAGES PREDICTS REGULATORY MIRNA-TF LOOPS AS NOVEL TARGETS OF PARASITE IMMUNE SUBVERSION

Gharsallah,

Lecoeur,

Varet

et al. 2024

Preprint

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MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level and play a crucial role in numerous disease processes, including infections. Although intracellular microbial pathogens are known to modulate host cell gene expression to establish permissive conditions for infection, the specific role of host-encoded miRNAs underlying such subversion remains poorly understood. In this study, we employed the protozoan parasite Leishmania amazonensis as a model system to investigate how infection of macrophages modifies the host cell miRNA profile to evade antimicrobial functions and to establish permissive conditions for intracellular proliferation. Dual RNA-seq analyses using matched mRNA and miRNA-enriched samples from uninfected and L. amazonensis-infected bone marrow-derived macrophages (BMDMs) revealed 102 differentially expressed miRNAs (padj<0.05), with 18 miRNAs showing reduced and 84 miRNAs showing increased abundance in infected BMDMs. Mapping putative networks of miRNA-mRNA interactions based on the observed expression changes, combined with Gene Ontology enrichment analyses, allowed us to identify potential miRNA target genes involved in key biological processes and metabolic pathways that permit parasite intracellular survival and proliferation. Our analyses predict the existence of a large miRNA-mRNA network affecting the expression level of numerous transcription factors that indicates inhibition of the NF-κB-dependent inflammatory response or the promotion of cholesterol biosynthesis during infection. In particular, the over 10e3-fold increase in the abundance of mmu-miR-686 in infected BMDMs was correlated with a reduced abundance of putative target transcripts implicated in miRNA biogenesis itself, in RNA binding, and in regulation of apoptosis, such as Caspase 12, the mRNA decay activator protein Zfp36l1 or Leukemia Inhibitory Factor Receptor Alpha. Likewise, the over 200-fold increase in abundance of mmu-miR-6546-3p was associated with a reduced abundance of putative target mRNAs implicated in cytokine-mediated signaling, positive regulation of apoptotic process and regulation of gene expression, affecting, for example, the MADS box transcription enhancer factor 2, the transformation related protein 53 inducible nuclear protein 1, or the G protein-coupled receptor 35. Interestingly, both miRNAs are predicted to simultaneously target 32 mRNAs that showed reduced abundance in infected BMDMs, including Maturin Neural Progenitor Differentiation Regulator (Mturn), a regulator of NF-κB transcription factor activity. In conclusion, our approach provides novel insight into molecular mechanisms that may govern macrophage subversion and intracellular Leishmania survival. Our results shed new light on the complex relationship among miRNAs, macrophage gene expression and Leishmania infection, proposing regulatory feed-forward loops (FFLs) and feedback loops (FBLs) between miRNAs and TFs as a novel target of Leishmania immune subversion. These findings open exciting new avenues for the development of intervention strategies aimed at disrupting such crucial interactions, for example using an anti-miR (antagomir) approach against mmu-miR-686 and mmu-miR-6546-3p.

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ARID3A plays a key regulatory role in palmitic acid‐stimulated milk fat synthesis in mouse mammary epithelial cells

Cited by 5 publications

References 36 publications

Methionine Promotes Milk Synthesis through the BRCC36-BRG1-mTOR Signaling Axis in Mammary Epithelial Cells

Methionine Promotes Milk Synthesis through the BRCC36-BRG1-mTOR Signaling Axis in Mammary Epithelial Cells

Comparative transcriptomic analysis of mammary gland tissues reveals the critical role of GPR110 in palmitic acid-stimulated milk protein and fat synthesis

MAPPING CHANGES OF MIRNA-MRNA NETWORKS INLEISHMANIA-INFECTEDMACROPHAGES PREDICTS REGULATORY MIRNA-TF LOOPS AS NOVEL TARGETS OF PARASITE IMMUNE SUBVERSION

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