Inflammation-related microRNA expression level in the bovine milk is affected by mastitis

Lai, Yu‐Chang; Fujikawa, T.; Maemura, Tadashi; Ando, Takaaki; Kitahara, Go; Endo, Yasuyuki; Yamato, Osamu; Koiwa, Masateru; Kubota, Chikara; Miura, Naoki

doi:10.1371/journal.pone.0177182

Cited by 61 publications

(49 citation statements)

References 57 publications

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“…Second, this population did not include subjects with nonmalignant mammary pathology such as mastitis or benign mammary tumors. This could be relevant as research evaluating miRNA in cow and porcine milk has identified particular miRNA signature that increase with mastitis, including miR‐21, miR‐146a, miR‐155, miR‐222, and miR‐383 26 . Fortunately, these miRNAs are not among the most relevant potential biomarkers identified in this dataset.…”

Section: Discussionmentioning

confidence: 93%

CirculatingmicroRNAas biomarkers of canine mammary carcinoma in dogs

Fish

Martinez‐Romero

DeInnocentes

et al. 2020

Veterinary Internal Medicne

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Background: Differentiating benign from canine malignant mammary tumors requires invasive surgical biopsy. Circulating microRNAs (miRNA) may represent promising minimally invasive cancer biomarkers in people and animals.Objectives: To evaluate the serum mRNA profile between dogs with and without mammary carcinoma, and to determine if any of these markers have prognostic significance.Animals: Ten healthy client-owned female dogs (5 intact, 5 spayed) and 10 dogs with histologically confirmed mammary carcinoma were included; 9 were client-owned, whereas 1 was a research colony dog.Methods: Retrospective study. Serum miRNA was evaluated by RNA deep-sequencing (RNAseq) and digital droplet PCR (dPCR).Expression of candidate biomarkers miR-18a, miR-19b, miR-29b, miR-34c, miR-122, miR-125a, and miR-181a was compared with clinical characteristics, including grade, metastasis, and survival.Results: 452 unique serum miRNAs were detected by RNAseq. Sixty-five individual miRNAs were differentially expressed (>±1.5-fold) and statistically significant between groups. Serum miR-19b (P = .003) and miR-125a (P < .001) were significantly higher in the mammary carcinoma group by dPCR. Both had high accuracy based on receiver operator characteristic area under the curve (0.930 for miR-125a; 0.880 for miR-19b). Circulating miR-18a by RNAseq was significantly higher in mammary carcinoma dogs with histologic evidence of lymphatic invasion (P = 0.03). There was no significant association with any miRNA and survival or inflammatory status. Conclusions and Clinical Importance: Circulating miRNAs are differentially expressed in dogs with mammary carcinoma. Serum miR-19b and miR-18a represent candidate biomarkers for diagnosis and prognosis, respectively. Abbreviations: AUC, area under the curve; CMT, canine mammary tumor(s); dPCR, digital droplet PCR; FAM, 6-carboxyfluorescein; miRs/miRNA, microRNA; qPCR, quantitative PCR; RNAseq, RNA deep-sequencing; ROC, receiver operator characteristic.

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Section: Discussionmentioning

confidence: 93%

CirculatingmicroRNAas biomarkers of canine mammary carcinoma in dogs

Fish

Martinez‐Romero

DeInnocentes

et al. 2020

Veterinary Internal Medicne

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“…Milk microRNAs are of particular importance because of their potential use as diagnostic, prognostic and functional tools in disease assessment and management (Alsaweed, Lai, Hartmann, Geddes, & Kakulas, ; Cui et al., ; Decmann et al., ; Iannaccone et al., ; Lai et al., , ; Markkandan et al., ; Melnik & Schmitz, ; Perge, Nagy, Decmann, Igaz, & Igaz, ; Schanzenbach, Kirchner, Ulbrich, & Pfaffl, ; Tome‐Carneiro et al., ). It is also of interest to study their impact in infant development in the context of infant formulas, which are poor in microRNAs (Alsaweed et al., ; Chen et al., ; Oh, Park, Son, & Kim, ), for newborns not fed with maternal milk (Oh et al., ; Zempleni et al., 2016).…”

Section: Milk Micrornas In Health and Diseasementioning

confidence: 99%

“…In milk, microRNA expression was related to mammary gland conditions, including infections (Iannaccone et al., ; Lai et al., , ; Sun et al., ), cancer (Decmann et al., ; Do Canto et al., ; Hesari et al., ), pregnancy and lactation status (Carney et al., ; Perri et al., ; Schanzenbach et al., ), and maternal diet (Chen et al., ). Therefore microRNAs in milk were studied for their potential as biomarkers (Gustafson, Tyryshkin, & Renwick, ; Melnik & Schmitz, ) such as quality controls of commercial milk (Oh et al., ).…”

Section: Milk Micrornas In Health and Diseasementioning

confidence: 99%

“…Some of the first links between milk microRNA and disease or development were explored in bovine milk in view of using milk microRNAs as biomarkers for mammary gland infections; especially mastitis (Lai et al., , ;), staphylococcus infection (Cai et al., ; Sun et al., ), and tuberculosis (Iannaccone et al., ). In these studies, immunity‐related microRNAs were overexpressed in milk samples from infected cows, thereby allowing their use as biomarkers of disease.…”

Section: Milk Micrornas In Health and Diseasementioning

confidence: 99%

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Milk MicroRNAs in Health and Disease

Benmoussa

Provost

2019

Comp Rev Food Sci Food Safe

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MicroRNAs are small noncoding RNAs responsible for regulating 40% to 60% of gene expression at the posttranscriptional level. The discovery of circulating microRNAs in several biological fluids opened the path for their study as biomarkers and long‐range cell‐to‐cell communication mediators. Their transfer between individuals in the case of blood transfusion, for example, and their high enrichment in milk have sparked the interest for microRNA transfer through diet, especially from mothers to infants during breastfeeding. The extension of such paradigm led to the study of milk microRNAs in the case of cow or goat milk consumption in adults. Here we provide a comprehensive critical review of the key findings surrounding milk microRNAs in human, cow, and goat milk among other species. We discuss the data on their biological properties, their use as disease biomarkers, their transfer between individuals or species, and their putative or verified functions in health and disease of infants and adult consumers. This work is based on all the literature available and integrates all the results, theories, debates, and validation studies available so far on milk microRNAs and related areas of investigations. We critically discuss the limitations and outline future aspects and avenues to explore in this rapidly growing field of research that could impact public health through infant milk formulations or new therapies. We hope that this comprehensive review of the literature will provide insight for all teams investigating milk RNAs’ biological activities and help ensure the quality of future reports.

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“…miR‐21, miR‐146a, and miR‐155 are well‐studied miRNAs implicated in the immune responses initiated by the Toll‐like receptor signal transduction pathways, and regulate the activation of the transcription factor nuclear factor kappa B (NF‐κB) . In our previous study, we demonstrated that these inflammation‐related miRNAs are affected by mastitis and that the miRNAs in milk have potential utility as biomarkers of bovine mastitis .…”

Section: Introductionmentioning

confidence: 99%

Bovine milk transcriptome analysis reveals microRNAs and RNU2 involved in mastitis

Lai

Lai²,

Rahman

et al. 2019

The FEBS Journal

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Mastitis is a common inflammatory infectious disease in dairy cows. To understand the microRNA (miRNA) expression profile changes during bovine mastitis, we undertook a genome-wide miRNA study of normal milk and milk that tested positive on the California mastitis test for bovine mastitis (CMT+). Twenty-five miRNAs were differentially expressed (23 miRNAs upregulated and two downregulated) during bovine mastitis relative to their expression in normal milk. Upregulated mature miR-1246 probably derived from a U2 small nuclear RNA rather than an miR-1246 precursor. The significantly upregulated miRNA precursors and RNU2 were significantly enriched on bovine chromosome 19, which is homologous to human chromosome 17. A gene ontology analysis of the putative mRNA targets of the significantly upregulated miRNAs showed that these miRNAs were involved in binding target mRNA transcripts and regulating target gene expression, and a Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the upregulated miRNAs were predominantly related to cancer and immune system pathways. Three novel miRNAs were associated with bovine mastitis and were relatively highly expressed in milk. We confirmed that one of the novel mastitis-related miRNAs was significantly upregulated using a digital PCR system. The differentially expressed miR-NAs were involved in human cancers, infections, and immune-related diseases. The genome-wide analysis of miRNA profiles in this study provides insight into bovine mastitis and inflammatory diseases. DatabasesThe miRNAseq generated for this study can be found in the Sequence Read Archive (SRA) under BioProject Number PRJNA421075 and SRA Study Number SRP126134 (https://www. ncbi.nlm.nih.gov/bioproject/PRJNA421075).

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Inflammation-related microRNA expression level in the bovine milk is affected by mastitis

Cited by 61 publications

References 57 publications

CirculatingmicroRNAas biomarkers of canine mammary carcinoma in dogs

CirculatingmicroRNAas biomarkers of canine mammary carcinoma in dogs

Milk MicroRNAs in Health and Disease

Bovine milk transcriptome analysis reveals microRNAs and RNU2 involved in mastitis

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