piRNAs as Potential Regulators of Mammary Gland Development and Pathology in Livestock
Simple Summary
Abstract
1. Introduction
2. The Process of Generating piRNAs
2.1. Primary Processing
2.2. Secondary Amplification
3. Characteristics and Functions of piRNAs
3.1. The Characteristics of piRNAs
3.2. The Role of piRNAs in Silencing Transposons and Stabilizing Genomes
3.3. Physiological Functions of piRNAs
3.4. Factors Regulating piRNAs
4. The Role of ncRNAs in Mammary Gland Development
5. Prospects for piRNAs in Livestock Animals
6. The Role of piRNAs in Breast Cancer
7. The Role of piRNAs in Inflammation
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Species | 5′-Terminal Enzyme | 3′-Terminal Enzyme | Key PIWI Protein | Reference |
---|---|---|---|---|
Nematodes | Uncertainty | Uncertainty | Plasticity-related gene 1 (PRG-1), plasticity-related gene 2 (PRG-2) | [29] |
Zebrafish | Phospholipase D family member 6 (PLD6) | Uncertainty | ZIWI, ZILI | [30,31] |
Drosophila | Zuc | Trimmer | PIWI, Argonaute 3 (Ago3), Aubergin(Aub) | [32,33] |
Mice | PLD6 | Poly(A)-specific ribonuclease-like domain containing 1 (PNLDC1) | MIWI, MIWI2, MILI | [34,35,36] |
Particular Year | miRNA | Research Target | Model Type | Outcomes | References |
---|---|---|---|---|---|
Mammary gland development | |||||
2007 | let-7 | Comma-Dβ | In vitro | Inhibited self-renewal capacity of progenitor cells and promoted differentiation. | [96] |
2014 | miR-21 | HC11, mice | In vivo and in vitro | Regulated mammary gland development and lactation. | [97] |
2012 | miR-30b | Mice | In vivo | Inhibited normal mammary gland development and lipid droplet accumulation. | [93] |
2020 | miR-31 | HC11, mice | In vivo and in vitro | Promoted MaSCS self-renewal, alveogenesis, and lipid droplet accumulation. | [94] |
2020 | miR-34a | Comma-Dβ, SUM159pt, mice | In vivo and in vitro | Inhibited MaSCs self-renewal, terminal end bud (TEB) development. | [98] |
2009 | miR-101a | HC11, mice | In vivo and in vitro | Inhibited HC11 proliferation and β-casein expression, affected mammary gland development and degeneration. | [99] |
2010 | miR-132, miR-212 | Mice | In vivo | Promoted ducts growth and modulated epithelial–stromal interactions. | [100] |
2015 | miR-137 | MDA-MB-231, 293T, mice | In vivo and in vitro | Promoted thickening of the mammary substrate. | [101] |
2006 | miR-138 | Mouse mammary epithelial cells, mice | In vivo and in vitro | Regulated mammary epithelial cell proliferation and mammary gland development, promoted β-casein expression. | [102] |
2017 | miR-139 | BMEC, Holstein cows | In vivo and in vitro | Inhibited β-casein synthesis and BMEC proliferation. | [103] |
2022 | miR-142-5p, miR-148C, miR-152, miR-218, | Goats | In vivo | Regulated mammary gland regenerative degeneration. | [104] |
2014 | miR-193b | MEC, mice | In vivo and in vitro | Inhibited mammary stem/progenitor cell activity and alveolar differentiation. | [105] |
2009 | miR-200c | 293T, Tera-2, mice | In vivo and in vitro | Inhibited mammary duct formation. | [106] |
2018 | miR-205 | MEC, mice | In vivo and in vitro | Impacted mammary regenerative capacity and mammary homeostasis. | [107] |
2019 | miR-489 | Mouse mammary epithelial cells, mice | In vivo and in vitro | Inhibited duct growth and TEB formation. | [108] |
Milk component synthesis | |||||
2018 | miR-15b | MCF-10A, mice, goats | In vivo and in vitro | Inhibited lipid synthesis and metabolism. | [109] |
2017 | miR-17-5p miR-148a | GMEC, goats | In vivo and in vitro | Promoted triacylglycerol (TAG) synthesis and milk fat droplet accumulation. | [110] |
2015 | miR-24 | GMEC, goats | In vivo and in vitro | Increased unsaturated fatty acid concentrations, TAG levels, and milk fat droplet accumulation. | [111] |
2018 | miR-25 | GMEC, goats | In vivo and in vitro | Inhibited TAG synthesis and lipid droplet accumulation. | [112] |
2013 | miR-27a | GMEC, goats | In vivo and in vitro | Inhibited TAG synthesis and reduced the ratio of unsaturated/saturated fatty acids. | [113] |
2015 | miR-29s | DCMEC, 293T, Chinese Holstein cows | In vivo and in vitro | Inhibited triglyceride, protein, and lactose secretion. | [114] |
2013 | miR-103 | GMEC, goats | In vivo and in vitro | Promoted lipid droplet accumulation and TAG accumulation. | [95] |
2011/2017 | miR-126-3p | MCF-10A, mice | In vivo and in vitro | Inhibited β-casein secretion and lipid synthesis. | [115,116] |
2019 | miR-142-3p | MMGEC, mice | In vivo and in vitro | Inhibited secretion of β-casein and TAG. | [117] |
2017 | miR-145 | GMEC, goats | In vivo and in vitro | Promoted lipid droplet enlargement and TAG accumulation, increased the relative content of unsaturated fatty acids. | [118] |
2016 | miR-150-5p | Mice | In vivo | Inhibited the de novo synthesis of lipids and fatty acids. | [119] |
2016 | miR-181b | GMEC, goats | In vivo and in vitro | Increased TAG levels and cream droplet accumulation. | [120] |
2020 | miR-204 | HC11, mice | In vivo and in vitro | Promoted β-casein and milk fat synthesis. | [88] |
2019 | miR-206 | HC11, mice | In vivo and in vitro | Promoted lipid accumulation. | [121] |
2018 | miR-221 | MEC, MCF-10A, mice | In vivo and in vitro | Promoted lipid synthesis. | [122] |
2015 | miR-486 | BMEC, Holstein cows | In vivo and in vitro | Promoted beta-casein, lactose, and lipid secretion. | [123] |
Particular Year | Detection Methods | Species | Outcomes | References |
---|---|---|---|---|
2021 | Small RNA-seq | Porcine | Characterization of the composition of piRNAs in spermatozoa suggests that piRNAs may be potential negative regulatory markers of sperm quality. | [135] |
2012 | Small RNA-seq, qRT-PCR | Porcine | It was demonstrated that piRNAs were predominantly enriched in the mature gonads and were expressed more in the testis than in the ovary. | [136] |
2023 | Small RNA-seq | Porcine | Expression of piRNAs is regulated by Senecavirus A (SVA) and promotes apoptosis. | [137] |
2015 | Small RNA-seq | Porcine | Characterization of the composition of piRNAs in testis suggests that mammalian piRNAs exist in the ping-pong cycle and have a role in the post-transcriptional regulation of protein-coding genes. | [130] |
2022 | Small RNA-seq | Xiang pigs | Identification of the composition of piRNAs in testicular tissues at different stages demonstrates that piRNAs regulate spermatogenesis. | [129] |
2017 | Small RNA-seq, qRT-PCR | Porcine | Characterization of the expression profiles of testicular piRNAs at different stages of sexual maturation demonstrated that piRNAs regulate testicular development and spermatogenesis. | [138] |
2012 | Small RNA-seq, qRT-PCR | Porcine | Evidence for a potential role of piRNAs in female germ cell development. | [139] |
2020 | Small RNA-seq, qRT-PCR | Porcine | Characterization of the expression profile of sperm plasma extracellular vesicles (SP-EVs) piRNAs suggests that piRNAs play a role in the physiological function of spermatozoa. | [140] |
2017 | Small RNA-seq, qRT-PCR | Bovids | The piRNAs in the testis were identified as longer than the piIRNAs in oocytes and embryos. | [141] |
2020 | Small RNA-seq | Yattle, cattle, yaks, | Promoter hypermethylation of PIWI/piRNA pathway genes leading to gene silencing and reduction in testis-thick piRNAs is a driver of bovine HMS. | [131] |
2015 | Small RNA-seq | Calves | Expression of piRNAs in bovine blood and plasma was revealed, suggesting that they may originate from tissues other than blood cells and thus enter the circulation. | [142] |
2018 | Small RNA-seq | Cattle, yaks, dzo | Comparison of the expression characteristics of three ruminant piRNAs provides theoretical references for exploring their regulatory mechanisms in spermatogenesis and dzo reproductive therapy. | [143] |
2020 | Small RNA-seq, qRT-PCR | Bulls | Expression of piRNAs in spermatozoa was detected, suggesting that they may play a role in embryonic development and may serve as biomarkers of semen fertility. | [144] |
2017 | Small RNA-seq | Bulls | Characterization of the composition of piRNAs in frozen spermatozoa suggests a role in sperm development and fertility. | [132] |
2015 | Small RNA-seq | Bovine | Detection of the composition of mature testicular and ovarian piRNAs revealed that ovarian piRNAs were very similar to spermatogenesis thick-walled stage piRNAs. | [145] |
2018 | Small RNA-seq | Bovids | Detection of milk exosomal piRNAs expression suggests that they may be related to immune and developmental functions. | [134] |
2021 | Small RNA-seq | Cattle | The presence of piRNAs in ejaculated sperm was confirmed, suggesting that they may regulate sperm maturation, fertilization process, and embryonic genome activation. | [146] |
2021 | Small RNA-seq | Bovids | Expression of piRNAs was detected separately in both milks, suggesting a possible regulatory role in calf immunity and development. | [147] |
2023 | Small RNA-seq | Murrah buffalo | Characterization of the composition of piRNAs at different stages of lactation implies that piRNAs can serve as potential targets for the regulation of lactation. | [148] |
2019 | Small RNA-seq | Mongolian horse | Characterization of piRNAs composition in sexually mature and immature testes suggests that piRNAs may regulate testicular development and spermatogenesis. | [149] |
2022 | Small RNA-seq | Sheep | Expression profiles of piRNAs in LP and FP ovaries were characterized to facilitate understanding of the role of piRNAs in the estrous cycle. | [133] |
2022 | Small RNA-seq | Sheep | Characterization of the composition of testicular piRNAs demonstrates that piRNAs may mediate blood–testis barrier stability and spermatogonial stem cell differentiation. | [150] |
2021 | Small RNA-seq | Sunite (SN), Small-tailed Han (STH) | Identification of differential expression of testicular piRNAs in different breeds suggests that piRNAs may be associated with male fecundity. | [151] |
2023 | Small RNA-seq, qRT-PCR | Tibetan sheep | Characterization of piRNAs expression profiles in different stages of testis suggests that piRNAs regulate male fertility and spermatogenesis. | [152] |
Particular Year | piRNA | Expression | Model Type | Species | Finding | References |
---|---|---|---|---|---|---|
2021 | piR-651 | Upregulation | In vivo and in vitro | Human | Bound to PIWIL2, promoted cell proliferation and migration through DNMT1-mediated methylation of the PTEN promoter. | [158] |
2021 | piR-823 | Upregulation | In vivo and in vitro | Human and mice | Increased the expression of DNMT1, DNMT3A, and DNMT3B genes to promote DNA methylation of APC genes to activate the Wnt signaling pathway. | [159] |
2022 | piR-823 | Upregulation | In vivo and in vitro | Human and mice | Inhibited piR-823 expression inhibited cell proliferation, PI3K/Akt/mTOR gene expression, and increased gene and protein expression of ERα. | [160] |
2013 | piR-932 | Upregulation | In vivo and in vitro | Human and mice | Bound to PIWIL2, promoted methylation of promoter CpG islands to repress Latexin expression. | [13] |
2023 | piR-2158 | Downregulation | In vivo and in vitro | Human and mice | Competed with FOSL1 to inhibit IL-11 expression and secretion, inactivating JAK/STAT signaling and thereby inhibiting breast cancer. | [18] |
2022 | piR-17560 | Upregulation | In vivo and in vitro | Human | Targeted FTO-mediated m6A demethylation enhances ZEB1 expression, thereby promoting chemotherapy resistance and EMT. | [161] |
2013 | piR-4987, piR-20365, piR-20485, piR-20582 | Upregulation | In vivo | Human | Influenced cancer development and lymph node metastasis. | [154] |
2017 | piR-1282, piR-21131, piR-23672, piR-26526, piR-26527, piR-26528, piR-30293, piR-32745 | Upregulation | In vivo | Human | Can be used as a biomarker for breast cancer and provided a therapeutic target. | [156] |
piR-23662 | Downregulation | |||||
2014 | piR-31106 | Upregulation | In vivo and in vitro | Human | Responded to cell growth, cell cycle progression, and hormonal signaling. | [155] |
2021 | piR-31106, piR-34998, piR-40067 | Upregulation | In vivo | Human | Can be used as a prognostic and therapeutic marker for breast cancer. | [157] |
2023 | piR-31106 | Upregulation | In vivo and in vitro | Human | Promoted cell proliferation and migration as well as oncogene expression and METTL3-mediated m6A methylation. | [162] |
2025 | piR-31115 | Upregulation | In vivo and in vitro | Human | Bound to PIWIL4 and inhibits the degradation of HSP90AA1 protein, thereby promoting cell migration. | [163] |
2020 | piR-31143 | Upregulation | In vivo and in vitro | Human | Can modulation of TNBC behavior through ERβ. | [164] |
2014 | piR-34377, piR-35407, piR-36743 | Upregulation | In vivo and in vitro | Human | Responded to cell growth, cell cycle progression, and hormonal signals. | [155] |
piR-36026, piR-36249, piR-36318, piR-36712 | Downregulation | |||||
2019 | piR-36712 | Downregulation | In vivo and in vitro | Human and mice | Knockdown of piR-36712 inhibits p53 activity through SEPW1, upregulates Slug/p21, and decreases E-calmodulin levels, ultimately inhibiting cell proliferation, migration, and invasion. | [165] |
2020 | piR-016658 | Upregulation | In vivo and in vitro | Human | Regulated by cell Cyclin D1, affects stem cell function. | [166] |
piR-016975 | Downregulation | |||||
2015 | piR-021285 | Upregulation | In vivo and in vitro | Human | Increases the methylation level of the ARHGAP11A gene, which promotes cell invasion and inhibits cell apoptosis. | [167] |
2015 | piR-sno75 | Upregulation | In vivo and in vitro | Human and mice | Binding to WDR5 recruits the MLL3/UTX complex to the TRAIL promoter region, thereby inducing H3K4 methylation and H3K27 demethylation. | [168] |
2022 | piR-MW557525 | Upregulation | In vivo and in vitro | Human | Promotes the proliferation, migration, and invasion of Piwil2-iCSCs, promotes the expression of CD24, CD133, KLF4, and SOX2, and inhibits apoptosis. | [169] |
2018 | piR-FTH1 | Downregulation | In vivo and in vitro | Human | Binds to HILI/HIWI2 and down-regulates FTH1, increasing sensitivity to chemotherapy. | [170] |
2024 | piR-YBX1 | Downregulation | In vivo and in vitro | Human and mice | Inhibition of YBX1 expression leads to inhibition of MEK and ERK1/2 MAPK signaling pathways, ultimately inhibiting cell proliferation and migration. | [171] |
Particular Year | piRNA | Expression | Research Target | Finding | References |
---|---|---|---|---|---|
2024 | hsa-piR-3411, hsa-piR-24541, hsa-piR-27080, hsa-piR-28104, hsa-piR-32157 and 10 others | Upregulation | Human peripheral venous blood | Identification of piRNAs in the plasma of CP patients demonstrated that piRNAs are associated with inflammation. | [189] |
hsa-piR-32835, hsa-piR-32836, hsa-piR-32986, hsa-piR-33168 | Downregulation | ||||
2022 | piRNA-6426 | Downregulation | Rat cardiomyocytes, rats | Inhibits secretion of inflammatory factors IL-1β and TNF-α, cardiomyocyte apoptosis, oxidative stress, and improves the inflammatory microenvironment in heart failure. | [186] |
2023 | piR-has-27620, piR-has-27124 | Upregulation | Blood samples | Identification of peripheral leukocyte piRNA expression and their enrichment in Rap1, PI3K-Akt, and MAPK pathways as RA biomarkers. | [190] |
2021 | rno-piR-017330 | Upregulation | Endothelial cells, rats | Identification of piRNAs expression in endothelial cells under inflammatory conditions suggests that piRNAs may regulate inflammatory processes. | [187] |
2024 | hsa_piR_019949 | Downregulation | C28/I2, SW1353 | Inhibition of NEAT1 and NLRP3 expression regulates the NOD-like receptor signaling pathway and modulates OA progression. | [185] |
2024 | mmu_piR_037459 | Upregulation | Mice cardiomyocytes, mice | Inhibition of collagenase II expression, promotion of chondrocyte apoptosis and inhibition of proliferation, inhibition of USP7 expression, and regulation of OA progression. | [188] |
2024 | piR-112710 | Downregulation | Mice cardiomyocytes, mice | Inhibits the Txnip/NLRP3 signaling pathway, reduces the levels of IL-18, IL-1β, and NLRP3, inhibits cardiomyocyte injury, and regulates inflammation progression. | [19] |
2025 | pir-has-216911 | Upregulation | HL7702, Huh7, HepG2, Hep3B, nude mice | Inhibition of the TLR4/NFκB/NLRP3 inflammatory signaling pathway suppressed the inflammatory response. | [183] |
2020 | piRNAs | Differential expression | Sudani duck | The composition of piRNAs in brain and lung was characterized, suggesting that they may be associated with lung inflammation. | [191] |
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Yu, W.; Zhang, Z.; Wang, Z.; Dong, X.; Hou, Q. piRNAs as Potential Regulators of Mammary Gland Development and Pathology in Livestock. Vet. Sci. 2025, 12, 594. https://doi.org/10.3390/vetsci12060594
Yu W, Zhang Z, Wang Z, Dong X, Hou Q. piRNAs as Potential Regulators of Mammary Gland Development and Pathology in Livestock. Veterinary Sciences. 2025; 12(6):594. https://doi.org/10.3390/vetsci12060594
Chicago/Turabian StyleYu, Wenjing, Zixuan Zhang, Zhonghua Wang, Xusheng Dong, and Qiuling Hou. 2025. "piRNAs as Potential Regulators of Mammary Gland Development and Pathology in Livestock" Veterinary Sciences 12, no. 6: 594. https://doi.org/10.3390/vetsci12060594
APA StyleYu, W., Zhang, Z., Wang, Z., Dong, X., & Hou, Q. (2025). piRNAs as Potential Regulators of Mammary Gland Development and Pathology in Livestock. Veterinary Sciences, 12(6), 594. https://doi.org/10.3390/vetsci12060594