Abstract：Bovine mammary epithelial cells (bMECs) are the main cell type of mammary gland, they not only play the role of lactation, but also regulate the innate immune response of mammary gland. The proliferation and apoptosis of bMECs are regulated by enzymes, hormones, cytokines and other molecules, it is a cellular metabolic process of breast tissue in a specific physiological environment and affects the development and function of breast. In order to explore the function of mammary gland in dairy cows(Bos taurus), a lot of studies on the proliferation and apoptosis of bMECs have been carried out in recent years, and excellent results have been achieved. This paper mainly introduces the signaling pathways related to the cell proliferation and apoptosis, and focuses on the latest research progress of the regulation mechanism of proliferation and apoptosis by coding and non-coding genes (miRNA, lncRNA and circRNA) in bMECs, so as to provide reference for the further research of molecular breeding of high-yield and anti-mastitis dairy cows.
[1] 古新宇. 2016. 甘氨酰tRNA合成酶对奶牛乳腺上皮细胞乳合成及细胞增殖的影响[D].硕士学位论文, 东北农业大学, 导师:高学军, pp. 29-35. (Gu X Y, 2016. Effect of Glycyl-tRNA synthetase on lactogenesis and cell proliferation of bovine mammary epithelial cells[D]. Thesis for M.S., Northeast Agricultural University, Supervisor: GAO X J, pp. 29-35.) [2] 胡祥维, 杨帅, 袁婧, 等. 2020. 敲低SQLE基因对奶牛乳腺上皮细胞增殖及凋亡的影响[J]. 中国畜牧兽医, 47(08): 2510-2517. (Hu X W, Yang S, Yuan J, et al.2020. Effect of SQLE gene knock-down on proliferation and apoptosis of dairy cow epithelial cells[J]. China Animal Husbandry & Veterinary Medicine, 47(08): 2510-2517.) [3] 华丽萍, 刘双行, 赵鑫哲, 等. 2020. DDR1对奶牛乳腺上皮细胞增殖与凋亡的调控作用[J]. 畜牧兽医学报, 51(09): 2109-2119. (Hua L P, Liu S X, Zhao X Z, et al.2020. Effect of interference and overexpression of DDR1 on proliferation and apoptosis of mammary epithelial cells in diary cows[J]. Acta Vterinaria et Zootechnica Sinica, 51(09): 2109-2119.) [4] 司雨. 2014. SND1基因对奶牛乳腺上皮细胞泌乳机能的影响[D].硕士学位论文, 东北农业大学, 导师: 高学军, pp. 28-41. (Si Y.2014. The effcet of SND1 gene on lactation fuction of dairy cow mammary epithelial cells[D]. Thesis for M.S., Northeast Agricultural University, Supervisor: GAO X J, pp. 28-41.) [5] 汤云飞. 2019. MMP9对奶牛乳腺上皮细胞泌乳功能的作用研究[D].硕士学位论文, 东北农业大学, 导师: 崔英俊, pp. 24-40. (Tang Y F, 2019. Research on the effect of MMP9 on lacting function of dairy cow mammary epithelial cell[D]. Thesis for M.S., Northeast Agricultural University, Supervisor: CUI Y J, pp. 24-40.) [6] 童超. 2017. 外泌体miRNA和lncRNA作为奶牛乳腺炎分子标记的筛选和功能鉴定[D].博士学位论文, 西北农林科技大学, 导师: 赵辛, pp.35-42. (Tong C.2017. Screening and characterization of exosomal miRNAs and lncRNAs as biomarkers in bovine mastitis[D]. Northwest A&F University, Thesis for Ph.D., Supervisor: Zhao X, pp. 35-42.) [7] 王兵兵. 2019. 环状RNA circLPP在奶牛乳腺炎组织中的表达及其作为潜在治疗靶点的应用分析[D].硕士学位论文, 西北农林科技大学, 导师: 高明清, pp. 19-30. (Wang B B.2019. Expression of circular RNA circLPP in bovine mastitis tissue and its application as a potential therapeutic target[D]. Northwest A&F University, Thesis for M.S., Supervisor: Gao M Q, pp. 19-30.) [8] 王伟华. 2019. FLCN调控奶牛乳腺上皮细胞增殖和乳蛋白合成的研究[D].硕士学位论文, 东北农业大学, 导师: 张娜, pp.24-32. (Wang W H.2019. Study on FLCN regulating mammary epithelial cell proliferation and milk protein synthesis in dairy cows[D]. Thesis for M.S., Northeast Agricultural University, Supervisor: Zhang N, pp. 24-32.) [9] 王媛. 2016. MiR-142-3p通过调控靶基因PTPN11影响乳腺上皮细胞MCF-10A的增殖[D].硕士学位论文, 东北农业大学, 导师: 王春梅, pp.25-32. (Wang Y.2016. MiR-142-3p influences the proliferation of MCF-10A by regulating target gene PTPN11[D]. Thesis for M.S., Northeast Agricultural University, Supervisor: Wang C M, pp. 25-32.) [10] 吴娟. 2009. 奶牛乳腺上皮细胞原代培养及TNF-α对其凋亡影响的研究[D].硕士学位论文, 内蒙古农业大学, 导师: 王凤龙, pp.24-34. (Wu J.2009. Primary culture of bovine mammary epithelial cells and effects of TNF-α on apoptosis of bovine mammary epithelial cells[D]. Thesis for M.S., Inner Mongolia Agricultural University, Supervisor: Wang F L, pp. 24-34.) [11] 杨兵. 2019. 奶牛乳腺差异表达长链非编码RNA的筛选、鉴定及其功能研究[D].博士学位论文, 西北农林科技大学, 导师: 王昕, pp.55-74. (Yang B.2019. Screening, identification and functional studies of long non-coding RNAs differentially expressed in mammary gland of diary cows[D].Northwest A&F University, Thesis for Ph.D., Supervisor: Wang X, pp. 55-74.) [12] 张彭媛. 2019. 环状RNA CircKIAA在奶牛乳腺炎组织中的表达及其在乳腺上皮细胞中的作用[D].硕士学位论文, 西北农林科技大学, 导师: 高明清, pp.22-29. (Zhang P Y.2019. Expression of circular RNA circKIAA in bovine mastitis tissue and its role in bovine mammary epithelial cells[D]. Northwest A&F University, Thesis for M.S., Supervisor: Gao M Q, pp. 22-29.) [13] 张芮琪. 2020. 环状RNA circ0001186在奶牛乳腺上皮细胞中的作用及分子机制[D].硕士学位论文, 西北农林科技大学, 导师: 徐永平, 高明清, pp.18-24. (Zhang R Q.2020. Functions and molecular mechanisms of circ0001186 in mammary epithelial cells of bovine.[D]. Northwest A&F University, Thesis for M.S., Supervisor: Xu Y P, Gao M Q, pp.18-24.) [14] Berryhill G E, Brust-Mascher I, Huynh J H, et al.2016. A convenient method for evaluating epithelial cell proliferation in the whole mammary glands of female mice[J]. Endocrinology Society, 157(10): 3742-3748. [15] Bian Y J, Lei Y, Wang C M, et al.2015. Epigenetic regulation of miR-29s affects the lactation activity of dairy cow mammary epithelial cells[J]. Journal of Cellular Physiology, 230(9): 2152-2163. [16] Cao Q Q, Li H H, Liu X, et al.2019. MiR-24-3p regulates cell proliferation and milk protein synthesis of mammary epithelial cells through menin in dairy cows[J]. Journal of Cellular Physiology, 234(2): 1522-1533. [17] Capuco A V, Wood D L, Baldwin R, et al.2001. Mammary cell number, proliferation, and apoptosis during a bovine lactation: relation to milk production and effect of bST[J]. Journal of Dairy Science, 84(10): 2177-2187. [18] Chai C, Song L J, Han S Y, et al.2018. MicroRNA-21 promotes glioma cell proliferation and inhibits senescence and apoptosis by targeting SPRY1 via the PTEN/PI3K/AKT signaling pathway[J]. CNS Neuroscience & Therapeutics, 24(5): 369-380. [19] Chen D Y, Yuan X H, Liu L J, et al.2018. Mitochondrial ATAD3A regulates milk biosynthesis and proliferation of mammary epithelial cells from dairy cow via the mTOR pathway[J]. Cell Biology International, 42(5): 533-542. [20] Chen K L, Li L, Li C M, et al.2019a. SIRT7 regulates lipopolysaccharide-induced inflammatory injury by suppressing the NF-κB signaling pathway[J]. Oxidative Medicine and Cellular Longevity, DOI: 10.1155/2019/3187972. [21] Chen P, Xu W T, Luo Y, et al.2017. MicroRNA 543 suppresses breast cancer cell proliferation, blocks cell cycle and induces cell apoptosis via direct targeting of ERK/MAPK[J]. Once Targets and Therapy, 10: 1423-1431. [22] Chen Z, Zhou J P, Wang M J, et al.2020. Circ09863 regulates unsaturated fatty acid metabolism by adsorbing miR-27a-3p in bovine mammary epithelial cells[J]. Journal of Agricultural and Food Chemistry, 68(32): 8589-8601. [23] Chen Z, Xu X, Tan T L, et al.2019b. MicroRNA-145 regulates immune cytokines via targeting FSCN1 in Staphylococcus aureus-induced mastitis in dairy cows[J]. Reproduction in Domestic Animals, 54(6): 882-891. [24] Chung S, Kim S H, Seo Y, et al.2017. Quantitative analysis of cell proliferation by a dye dilution assay: Application to cell lines and cocultures[J].Journal of the International Society for Advancement of Cytometry, 91(7): 704-712. [25] Creamer B A, Sakamoto K, Schmidt J W, et al.2010. Stat5 promotes survival of mammary epithelial cells through transcriptional activation of a distinct promoter in Akt1[J]. Molecular and Cellular Biology, 30(12): 2957-2970. [26] Cui Y J, Sun X, Jin L F, et al.2017. MiR-139 suppresses beta-casein synthesis and proliferation in bovine mammary epithelial cells by targeting the GHR and IGF1R signaling pathways[J]. BMC Veterinary Research, 13(1): 350. [27] Dai H, Wang C M, Yu Z H, et al.2018. MiR-17 regulates prostate cancer cell proliferation and apoptosis through inhibiting JAK-STAT3 signaling pathway[J]. Cancer Biotherapy and Radiopharmaceuticals, 33(3): 103-109. [28] Feng J W, Dang Y P, Zhang W Q, et al.2019. PTEN arginine methylation by PRMT6 suppresses PI3K-AKT signaling and modulates pre-mRNA splicing[J]. Proceedings of the National Academy Sciences of the USA, 116(14): 6868-6877. [29] Ferreira A M, Bislev S L, Bendixen E, et al.2013. The mammary gland in domestic ruminants: A systems biology perspective[J]. Journal of Proteomics, 94: 110-123. [30] Fiorentino F P, Bagella L, Marchesi I.2018. A new parameter of growth inhibition for cell proliferation assays[J]. Journal of Cellular Physiology, 233(5): 4106-4115. [31] Gajewska M, Motyl T.2004. IGF-binding proteins mediate TGF-β1-induced apoptosis in bovine mammary epithelial BME-UV1 cells[J]. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 139(1-3): 65-75. [32] Gilbert F B, Cunha P, Jensen K, et al.2013. Differential response of bovine mammary epithelial cells to Staphylococcus aureus or Escherichia coli agonists of the innate immune system[J]. Veterinary Research, 44: 40. [33] Gondaira S, Higuchi H, Iwano H, et al.2018. Innate immune response of bovine mammary epithelial cells to Mycoplasma bovis[J]. Journal of Veterinary Science, 19(1): 79. [34] Green K A, Streuli C H.2004. Apoptosis regulation in the mammary gland[J]. Cellular and Molecular Life Sciences, 61(15): 1867-1883. [35] Hombach S, Kretz M, 2016. Non-coding RNAs: Classification, biology and functioning[J]. Advances in Experimental Medicine and Biology, 937: 3-17. [36] Hou X M, Hu H L, Lin Y, et al.2016a. The effect of G protein-coupled receptor kinase 2 (GRK2) on lactation and on proliferation of mammary epithelial cells from dairy cows[J]. Journal of Dairy Science, 99(7): 5828-5836. [37] Hou X M, Lin L, Xing W N, et al.2016b. Spleen tyrosine kinase regulates mammary epithelial cell proliferation in mammary glands of dairy cows[J]. Journal of Dairy Science, 99(5): 3858-3868. [38] Hou Y, Feng F, Yang R.2020. Effect of miR-449a-mediated Notch signaling pathway on the proliferation, apoptosis and invasion of papillary thyroid carcinoma cells[J]. Oncology Reports, 43(2): 471-480. [39] Hsiao K Y, Sun H S, Tsai S J.2017. Circular RNA-New member of noncoding RNA with novel functions[J]. Experimental Biology and Medicine (Maywood, N.J.), 242(11): 1136-1141. [40] Hu B H, Song W J, Tang Y J, et al.2019. Induction of chemerin on autophagy and apoptosis in dairy cow mammary epithelial cells[J]. Animals (Basel), 9(10): 848. [41] Huang X, Zang Y L, Zhang M H, et al.2017. Nuclear factor of κB1 is a key regulator for the transcriptional activation of milk synthesis in bovine mammary epithelial cells[J]. DNA and Cell Biology, 36(4): 295-302. [42] Huang Y L, Zhao F, Luo C C, et al.2013. SOCS3-mediated blockade reveals major contribution of JAK2/STAT5 signaling pathway to lactation and proliferation of dairy cow mammary epithelial cells in vitro[J]. Molecules, 18(10): 12987-13002. [43] Jason S L, Yu, Wei C, et al, 2016. Proliferation, survival and metabolism: The role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination[J]. Development, 143(17): 3050-60. [44] Jeong W, Bae H, Lim W, et al.2017. The functional effects and mechanisms by which fibroblast growth factor 2 (FGF2) controls bovine mammary epithelial cells: Implications for the development and functionality of the bovine mammary gland[J]. Journal of Animal Science, 95(12): 5365-5377. [45] Jiang L, Zhao X H, Mao Y L, et al.2019. Long non-coding RNA RP11-468E2.5 curtails colorectal cancer cell proliferation and stimulates apoptosis via the JAK/STAT signaling pathway by targeting STAT5 and STAT6[J]. Journal of Experimental & Clinical Cancer Research:CR, 38(1):465. [46] Jiao B L, Zhang X L, Wang S H, et al.2019. MicroRNA-221 regulates proliferation of bovine mammary gland epithelial cells by targeting the STAT5a and IRS1 genes[J]. Journal of Dairy Science, 102(1): 426-435. [47] Kurita Y, Wada H.2011. Evidence that gastropod torsion is driven by asymmetric cell proliferation activated by TGF-β signaling[J]. Biology Letters, 7(5): 759-762. [48] Leibowitz B J, Cohick W S.2009. Endogenous IGFBP-3 is required for both growth factor-stimulated cell proliferation and cytokine-induced apoptosis in mammary epithelial cells[J]. Journal of Cellular Physiology, 220(1): 182-188. [49] Li C M, Li L, Chen K L, et al.2019a. UFL1 alleviates lipopolysaccharide-induced cell damage and inflammation via regulation of the TLR4/NF-κB pathway in bovine mammary epithelial cells[J]. Oxidative Medicine and Cellular Longevity, DOI: 10.1155/2019/6505373. [50] Li B, Xi P P, Wang Z L, et al.2018. PI3K/Akt/mTOR signaling pathway participates in Streptococcus uberis-induced inflammation in mammary epithelial cells in concert with the classical TLRs/NF-κB pathway[J]. Veterinary Microbiology, 227: 103-111. [51] Li D, Xie X J, Wang J, et al.2015. MiR-486 regulates lactation and targets the PTEN gene in cow mammary glands[J]. PLOS ONE, 10(3): e118284. [52] Li H M, Wang C M, Li Q Z, et al.2012. MiR-15a decreases bovine mammary epithelial cell viability and lactation and regulates growth hormone receptor expression[J]. Molecules, 17(10): 12037-12048. [53] Li L, Liu L J, Qu B, et al.2017. Twinfilin 1 enhances milk bio-synthesis and proliferation of bovine mammary epithelial cells via the mTOR signaling pathway[J]. Biochemical and Biophysical Research Communications, 492(3): 289-294. [54] Li S S, Teng S S, Xu J Q, et al.2019b. Microarray is an efficient tool for circRNA profiling[J]. Briefings in Bioinformatics, 20(4): 1420-1433. [55] Li S F, Zhou Y, Zheng X D, et al.2016. Sphk1 promotes breast epithelial cell proliferation via NF-κB-p65-mediated cyclin D1 expression[J]. Oncotarget, 7(49): 80579-80585. [56] Li X Z, Wang H, Zhang Y F, et al.2019c. Overexpression of lncRNA H19 changes basic characteristics and affects immune response of bovine mammary epithelial cells[J]. PeerJ, 7: e6715. [57] Li X R, Zhang P Y, Wang B B, et al.2019d. NDRG1 negatively regulates proliferation and milk bio-synthesis of bovine epithelial cells via the mTOR signaling pathway[J]. Research in Veterinary Science, 124: 158-165. [58] Li Y, Su X M, Pan H X.2019e. Inhibition of lncRNA PANDAR reduces cell proliferation, cell invasion and suppresses EMT pathway in breast cancer[J]. Cancer Biomarks: Section A of Disease Markers, 25(2): 185-192. [59] Li Y W, Cao Y, Wang J X, et al.2020. Kp-10 promotes bovine mammary epithelial cell proliferation by activating GPR54 and its downstream signaling pathways[J]. Journal of Cellular Physiology, 235(5): 4481-4493. [60] Lin Q, Chen H, Zhang M, et al.2019. Knocking down FAM83B inhibits endometrial cancer cell proliferation and metastasis by silencing the PI3K/AKT/mTOR pathway[J]. Biomedicine & Pharmacotherapy, 115: 108939. [61] Liu J, Zhang M L, Li D W, et al.2020a. Prolactin-responsive circular RNA circHIPK3 promotes proliferation of mammary epithelial cells from dairy cow[J]. Genes, 11(3): 336. [62] Liu X C, Yang Y W, Jiang P, et al.2018. Effect of QSOX1 on cattle carcass traits as well as apoptosis and triglyceride production in bovine fetal fibroblasts and mammary epithelial cells[J]. The Journal of Veterinary Medical Science, 80(8): 1329-1336. [63] Liu Y H, Hou J X, Zhang M, et al.2020b. Circ-016910 sponges miR-574-5p to regulate cell physiology and milk synthesis via MAPK and PI3K/AKT-mTOR pathways in GMECs[J]. Journal of Cellular Physiology, 235(5): 4198-4216. [64] Liu Y, Wang X M, Zhen Z, et al.2019. GRP78 regulates milk biosynthesis and the proliferation of bovine mammary epithelial cells through the mTOR signaling pathway[J]. Cellular & Molecular Biology Letters, 24: 57. [65] Long E, Lazaris-Karatzas A, Karatzas C, et al.2001. Overexpressing eukaryotic translation initiation factor 4E stimulates bovine mammary epithelial cell proliferation[J]. The International Journal of Biochemistry & Cell Biology, 33(2): 133-141. [66] Luo L H, Rao L, Luo L F, et al.2020. Long non-coding RNA NKILA inhibited angiogenesis of breast cancer through NF-κB/IL-6 signaling pathway[J]. Microvascular Research, 129: 103928. [67] Luoreng Z M, Wang X P, Mei C G, et al.2018. Comparison of microRNA profiles between bovine mammary glands infected with Staphylococcus aureus and Escherichia coli[J]. International Journal of Biological Sciences, 14(1): 87-99. [68] Ma M R, Pei Y F, Wang X X, et al.2019. LncRNA XIST mediates bovine mammary epithelial cell inflammatory response via NF-κB/NLRP3 inflammasome pathway[J]. Cell Proliferation, 52(1): e12525. [69] Pu J H, Li R, Zhang C L, et al.2017. Expression profiles of miRNAs from bovine mammary glands in response to Streptococcus agalactiae-induced mastitis[J]. The Journal of Dairy Research, 84(3): 300-308. [70] Rossi M, Bucci G, Rizzotto D, et al.2019. LncRNA EPR controls epithelial proliferation by coordinating Cdkn1a transcription and mRNA decay response to TGF-β[J]. Nature Communications, 10(1): 1969. [71] Safa A, Abak A, Shoorei H, et al.2020. MicroRNAs as regulators of ERK/MAPK pathway: A comprehensive review[J]. Biomedicine & Pharmacotherapy, 132: 110853. [72] Sakamoto K, Creamer B A, Triplett A A, et al.2007. The Janus Kinase 2 is required for expression and nuclear accumulation of Cyclin D1 in proliferating mammary epithelial cells[J]. Molecular Endocrinology, 21(8): 1877-1892. [73] Sang M J, Wu M, Meng L J, et al.2020. Identification of epithelial-mesenchymal transition-related circRNA-miRNA-mRNA ceRNA regulatory network in breast cancer[J]. Pathology, Research and Practice, 216(9): 153088. [74] Shao T R, Zheng Z N, Chen Y C, et al.2019. LncRNA AC007271.3 promotes cell proliferation, invasion, migration and inhibits cell apoptosis of OSCC via the Wnt/beta-catenin signaling pathway[J]. Life Sciences, 239: 117087. [75] Shen B L, Pan Q Q, Yang Y W, et al.2017. MiR-224 affects mammary epithelial cell apoptosis and triglyceride production by downregulating ACADM and ALDH2 genes[J]. DNA and Cell Biology, 36(1): 26-33. [76] Shi K R, Liu X, Li H H, et al.2017. Menin modulates mammary epithelial cell numbers in bovine mammary glands through Cyclin D1[J]. Journal of Mammary Gland Biology and Neoplasia, 22(4): 221-233. [77] Sun Y, Li L, Wu J, et al.2015a. Bovine recombinant lipopolysaccharide binding protein (BRLBP) regulated apoptosis and inflammation response in lipopolysaccharide-challenged bovine mammary epithelial cells (BMEC)[J]. Molecular Immunology, 65(2): 205-214. [78] Sun Y, Liu W Z, Liu T, et al.2015b. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis[J]. Journal of Receptors and Signal Transduction, 35(6): 600-604. [79] Szperka M E, Connor E E, Paape M J, et al.2005. Sequencing, chromosomal mapping, and functional characterization of bovine FLICE-Like Inhibitory Protein (FLIP)[J]. Cytogenetic and Genome Research, 112(1-2): 90-97. [80] Tang B, Liang W J, Liao Y, et al.2019. PEA15 promotes liver metastasis of colorectal cancer by upregulating the ERK/MAPK signaling pathway[J]. Oncology Reports, 41(1): 43-56. [81] Tang H L, Yang P, Yang X J, et al.2020. Growth factor receptor bound protein-7 regulates proliferation, cell cycle, and mitochondrial apoptosis of thyroid cancer cells via MAPK/ERK signaling[J]. Molecular and Cellular Biochemistry, 472(1-2): 209-218. [82] Turchinovich A, Weiz L, Langheinz A, et al.2011. Characterization of extracellular circulating microRNA[J]. Nucleic Acids Research, 39(16): 7223-7233. [83] Wang H, Wang X X, Li X R, et al.2019. A novel long non-coding RNA regulates the immune response in MAC-T cells and contributes to bovine mastitis[J]. The FEBS Journal, 286(9): 1780-1795. [84] Wang M Z, Jing Y J, Hu L Y, et al.2015. Recent advances on the circadian gene PER2 and metabolic rhythm of lactation of mammary gland[J]. Animal Nutrition, 1(4): 257-261. [85] Wang X X, Wang H, Zhang R Q, et al.2020a. LRRC75A antisense lncRNA1 knockout attenuates inflammatory responses of bovine mammary epithelial cells[J]. International Journal of Biological Sciences, 16(2): 251-263. [86] Wang Y M, Gao C, Zhang Y F, et al.2016. Visfatin stimulates endometrial cancer cell proliferation via activation of PI3K/Akt and MAPK/ERK1/2 signalling pathways[J]. Gynecologic Oncology, 143(1): 168-178. [87] Wang Y F, Jie L, Gong H F, et al.2020b. MiR-30 inhibits proliferation of trophoblasts in preeclampsia rats partially related to MAPK/ERK pathway[J]. Experimental and Therapeutic Medicine, 20(2): 1379-1384. [88] Wang Z R, Hou X M, Qu B, et al.2014. Pten regulates development and lactation in the mammary glands of dairy cows[J]. PLOS ONE, 9(7): e102118. [89] Wawryk-Gawda E, Chylińska-Wrzos P, Lis-Sochocka M, et al.2014. P53 protein in proliferation, repair and apoptosis of cells[J]. Protoplasma, 251(3): 525-533. [90] Xin P, Xu X Y, Deng C J, et al.2020. The role of JAK/STAT signaling pathway and its inhibitors in diseases[J]. International Immunopharmacology, 80: 106210. [91] Xu H C, Wang C Y, Song H Y, et al.2019a. RNA-Seq profiling of circular RNAs in human colorectal cancer liver metastasis and the potential biomarkers[J]. Molecular Cancer, 18(1): 8. [92] Xu J Z, Shao C C, Wang X J, et al.2019b. CircTADA2As suppress breast cancer progression and metastasis via targeting miR-203a-3p/SOCS3 axis[J]. Cell Death & Disease, 10(3): 175. [93] Yang Y W, Pan Q Q, Sun B X, et al.2016. MiR-29b targets LPL and TDG genes and regulates apoptosis and triglyceride production in MECs[J]. DNA Cell Biology, 35(12): 758-765. [94] Yang Y W, Fang X B, Yang R J, et al.2018. MiR-152 regulates apoptosis and triglyceride production in MECs via targeting ACAA2 and HSD17B12 genes[J]. Scientific Reports, 8(1): 417. [95] Yu Y B, Zhen Z, Qi H, et al.2019. U2AF65 enhances milk synthesis and growth of bovine mammary epithelial cells by positively regulating the mTOR-SREBP-1c signaling pathway[J]. Cell Biochemistry and Function, 37(2): 93-101. [96] Yuan X H, Zhen Z, Zhang M H, et al.2019. Cyclase-associated protein 1 is a key negative regulator of milk synthesis and proliferation of bovine mammary epithelial cells[J]. Cell Biochemistry and Function, 37(3): 185-192. [97] Zeng B, Chen T, Xie M Y, et al.2019. Exploration of long non-coding RNA in bovine milk exosomes and their stability during digestion in vitro[J]. Journal of Dairy Science, 102(8): 6726-6737. [98] Zhang M H, Chen D Y, Zhen Z, et al.2018. Annexin A2 positively regulates milk synthesis and proliferation of bovine mammary epithelial cells through the mTOR signaling pathway[J]. Journal of Cellular Physiology, 233(3): 2464-2475. [99] Zhang M, Ma L, Liu Y H, et al.2020. CircRNA-006258 sponge-adsorbs miR-574-5p to regulate cell growth and milk synthesis via EVI5L in goat mammary epithelial cells[J]. Genes, 11(7): 718. [100] Zhang X Y, Mao L.2021. Circular RNA Circ_0000442 acts as a sponge of miR-148b-3p to suppress breast cancer via PTEN/PI3K/Akt signaling pathway[J]. Gene, 766: 145113. [101] Zhang X L, Cheng Z X, Wang L X, et al.2019. MiR-21-3p centric regulatory network in dairy cow mammary epithelial cell proliferation[J]. Journal of Agricultural and Food Chemistry, 67(40): 11137-11147. [102] Zhou J, Xia L, Zhang Y.2019a. Naringin inhibits thyroid cancer cell proliferation and induces cell apoptosis through repressing PI3K/AKT pathway[J]. Pathology Research Practice, 215(12): 152707. [103] Zhou G, Yang J, Song P.2019b. Correlation of ERK/MAPK signaling pathway with proliferation and apoptosis of colon cancer cells[J]. Oncology Letters, 17(2): 2266-2270. [104] Zhu C, Jiang Y, Zhu J R, et al.2020. CircRNA8220 sponges miR-8516 to regulate cell viability and milk synthesis via Ras/MEK/ERK and PI3K/AKT/mTOR pathways in goat mammary epithelial cells[J]. Animals, 10(8): 1347.
