MicroRNA-152 Regulates DNA Methyltransferase 1 and Is Involved in the Development and Lactation of Mammary Glands in Dairy Cows

Abstract

MicroRNAs (miRNAs) are a class of small non-coding, endogenous regulatory RNAs that function by controlling gene expression at the post-transcriptional level. Using small RNA sequencing and qRT-PCR techniques, we found that the expression of miR-152 was significantly increased during lactation in the mammary glands of dairy cows producing high quality milk compared with that in cows producing low quality milk. Furthermore, DNA methyltransferase 1 (DNMT1), which is a target of miR-152, was inversely correlated with the expression levels of miR-152 in the mammary glands of dairy cows. Dairy cow mammary epithelial cells (DCMECs) were used as in vitro cell models to study the function of miR-152. The forced expression of miR-152 in DCMECs resulted in a marked reduction of DNMT1 at both mRNA and protein levels. This in turn led to a decrease in global DNA methylation and increased the expression of two lactation-related genes, serine/threonine protein kinase Akt (Akt) and peroxisome proliferator-activated receptor gamma (Pparγ). In contrast, inhibition of miR-152 showed the opposite results. By using an electronic Coulter counter (CASY-TT) and flow cytometer, we discovered that miR-152 enhanced the viability and multiplication capacity of DCMECs. In conclusion, miR-152 plays an important role in the development and lactation processes in the mammary glands of dairy cows. Our data provide insights into dairy cow mammary gland development and lactation.

DNMT1 activates the canonical Wnt signaling in rheumatoid arthritis model rats via a crucial functional crosstalk between miR-152 and the DNMT1, MeCP2

“…The miR-323-3p was identified as a positive regulator of Wnt signaling in RA FLS, suggesting its potential pathogenic involvement and future use as a therapeutic target for RA patients. MiR-152 is a candidate involved in the interaction between miRNA and DNA methylation [36][37][38][39]. A recent report suggests that miR-152 is frequently down-regulated and regulates the DNMT1 expression in the hepatitis B virus-related hepatocellular carcinoma.…”

Milk MicroRNAs in Health and Disease

“…The majority of studies have only investigated this matter in silico using microRNA‐target identification tools and associated pathways/gene ontology analysis (Alsaweed et al., , ; Cai et al., , ; Carney et al., ; Chen et al., , , ; Chokeshaiusaha, Sananmuang, Puthier, & Nguyen, ; Do, Li, Dudemaine, & Ibeagha‐Awemu, ; Golan‐Gerstl, Elbaum Shiff, et al., ; Gu et al., , ; Hou et al., ; Kang et al., ; Li et al., , ; Liao et al., ; Liu et al., ; Lukasik & Zielenkiewicz, ; Modepalli et al., ; Munch et al., ; Shen et al., ; Simpson et al., ; Sun et al., ; Wang et al., ; Zhang et al., ; Zhou et al., ).…”

“…More than seven papers have confirmed the repression of DNA methyl transferase 1 (DNMT1) by miR‐148a, using reliable methodologies including reporter‐gene assays, western blots and RT‐qPCR (Chou et al., ). Milk also contains other conserved microRNAs that can regulate DNMT1 like milk miR‐152 (Liu et al., ; Wang et al., ).…”

Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions

“…PXR expression is regulated also by miR-148a. The miRNA-dependent regulation of several epigenetic enzymes including DNMTs, HDACs, EZH2, and epigenetic enzymes that regulate miRNA-specifying genes (which produce miRNA precursor transcripts) have been reported [104, 105]. Such cross talks provide a miRNA-dependent additional regulatory cascades that may alter DME/transporter expression.…”