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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 1
Jan.  2021
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Article Contents

Effects of different subtypes of Numb protein subtypes on liver fibrosis-related signaling pathways

DOI: 10.3969/j.issn.1001-5256.2021.01.036
  • Received Date: 2020-07-28
  • Accepted Date: 2020-08-28
  • Published Date: 2021-01-20
  • Liver fibrosis is the only way for various chronic liver diseases to develop into liver cirrhosis and is a reversible pathological state. However, how to prevent or reverse the development and progression of liver fibrosis is still an important scientific problem to be solved in clinical practice. As an important cell fate determinant, Numb has been shown to be closely associated with the development of many diseases. In the fibrotic environment, different subtypes of Numb protein are translated due to the selective shear action of the Numb gene, which have different regulatory effects on the activation of different signaling pathways and the differentiation of liver stem cells. At present, there are few reports on the role of Numb protein subtypes in liver fibrosis. This article reviews the regulatory effect of different Numb protein subtypes on the Notch, Hedgehog, and P53 signaling pathways and liver stem cells and elaborates on their potential application prospects in the treatment of liver fibrosis.

     

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  • [1]
    BOTTCHER K, PINZANI M. Pathophysiology of liver fibrosis and the methodological barriers to the development of anti-fibrogenic agents[J]. Adv Drug Deliv Rev, 2017, 1(121): 3-8. http://www.sciencedirect.com/science/article/pii/S0169409X17300728
    [2]
    HIGASHI T, FRIEDMAN SL, HOSHIDA Y. Hepatic stellate cells as key target in liver fibrosis[J]. Adv Drug Deliv Rev, 2017, 1(121): 27-42. http://www.ncbi.nlm.nih.gov/pubmed/28506744/
    [3]
    MORAN-SALVADOR E, MANN J. Epigenetics and liver fibrosis[J]. Cell Mol Gastroenterol Hepatol, 2017, 4(1): 125-134. DOI: 10.1016/j.jcmgh.2017.04.007
    [4]
    GULINO A, di MARCOTULLIO L, SCREPANTI I. The multiple functions of Numb[J]. Exp Cell Res, 2010, 316(6): 900-906. DOI: 10.1016/j.yexcr.2009.11.017
    [5]
    WU J, SHEN SL, CHEN B, et al. Numb promotes cell proliferation and correlates with poor prognosis in hepatocellular carcinoma[J]. PLoS One, 2014, 9(4): e95849. DOI: 10.1371/journal.pone.0095849
    [6]
    JADHAV S, AJAY AK, TRIVEDI P, et al. RNA- binding protein musashi homologue 1 regulates kidney fibrosis by translational inhibition of p21 and numb mRNA[J]. J Biol Chem, 2016, 291(27): 14085-14094. DOI: 10.1074/jbc.M115.713289
    [7]
    RHYU MS, JAN LY, JAN YN. Asymmetric distribution of numb protein during division of the sensory organ precursor cell confers distinct fates to daughter cells[J]. Cell, 1994, 76(3): 477-491. DOI: 10.1016/0092-8674(94)90112-0
    [8]
    CONFALONIERI S, COLALUCA IN, BASILE A, et al. Exon 3 of the numb gene emerged in the chordate lineage coopting the numb protein to the regulation of MDM2[J]. G3 (Bethesda), 2019, 9(10): 3359-3367. DOI: 10.1534/g3.119.400494
    [9]
    ZHOU Y, ABAGYAN R. How and why phosphotyrosine-containing peptides bind to the SH2 and PTB domains[J]. Fold Des, 1998, 3(6): 513-22. DOI: 10.1016/S1359-0278(98)00067-4
    [10]
    VERDI JM, BASHIRULLAH A, GOLDHAWK DE, et al. Distinct human Numb isoforms regulate differentiation vs. proliferation in the neuronal lineage[J]. Proc Natl Acad Sci U S A, 1999, 96(18): 10472-10476. DOI: 10.1073/pnas.96.18.10472
    [11]
    BERES BJ, GEORGE R, LOUGHER EJ, et al. Numb regulates Notch1, but not Notch3, during myogenesis[J]. Mech Dev, 2011, 128(5-6): 247-257. DOI: 10.1016/j.mod.2011.02.002
    [12]
    HUANG M, CHANG A, CHOI M, et al. Antagonistic interaction between Wnt and Notch activity modulates the regenerative capacity of a zebrafish fibrotic liver model[J]. Hepatology, 2014, 60(5): 1753-1766. DOI: 10.1002/hep.27285
    [13]
    JUNG KH, ZHANG J, ZHOU C, et al. Differentiation therapy for hepatocellular carcinoma: Multifaceted effects of miR-148a on tumor growth and phenotype and liver fibrosis[J]. Hepatology, 2016, 63(3): 864-879. DOI: 10.1002/hep.28367
    [14]
    GUO Y, ZHANG K, CHENG C, et al. Numb (-low) enriches a castration-resistant prostate cancer cell subpopulation associated with enhanced notch and hedgehog signaling[J]. Clin Cancer Res, 2017, 23(21): 6744-6756. DOI: 10.1158/1078-0432.CCR-17-0913
    [15]
    FLORES AN, McDERMOTT N, MEUNIER A, et al. Numb inhibition of NOTCH signalling as a therapeutic target in prostate cancer[J]. Nat Rev Urol, 2014, 11(9): 499-507. DOI: 10.1038/nrurol.2014.195
    [16]
    HWANG WL, YANG MH. Numb is involved in the non-random segregation of subcellular vesicles in colorectal cancer stem cells[J]. Cell Cycle, 2016, 15(20): 2697-703. DOI: 10.1080/15384101.2016.1218101
    [17]
    AIMAITI Y, YUSUFUKADIER M, LI W, et al. TGF-β1 signaling activates hepatic stellate cells through Notch pathway[J]. Cytotechnology, 2019, 71(5): 881-891. DOI: 10.1007/s10616-019-00329-y
    [18]
    BANSAL R, van BAARLEN J, STORM G, et al. The interplay of the Notch signaling in hepatic stellate cells and macrophages determines the fate of liver fibrogenesis[J]. Sci Rep, 2015, 5: 18272. http://europepmc.org/articles/PMC4677309/
    [19]
    YONGPING M, ZHANG X, XUEWEI L, et al. Astragaloside prevents BDL-induced liver fibrosis through inhibition of notch signaling activation[J]. J Ethnopharmacol, 2015, 169: 200-209. DOI: 10.1016/j.jep.2015.04.015
    [20]
    LI J, DONG S, YE M, et al. MicroRNA-489-3p represses hepatic stellate cells activation by negatively regulating the JAG1/Notch3 signaling pathway[J]. Dig Dis Sci, 2020.[Online ahead of print]
    [21]
    COUTURIER L, VODOVAR N, SCHWEISGUTH F. Endocytosis by Numb breaks Notch symmetry at cytokinesis[J]. Nat Cell Biol, 2012, 14(2): 131-139. DOI: 10.1038/ncb2419
    [22]
    KANDACHAR V, ROEGIERS F. Endocytosis and control of Notch signaling[J]. Curr Opin Cell Biol, 2012, 24(4): 534-540. DOI: 10.1016/j.ceb.2012.06.006
    [23]
    BERDNIK D, TOROK T, GONZÁLEZ-GAITÁN M, et al. The endocytic protein alpha-Adaptin is required for numb-mediated asymmetric cell division in Drosophila[J]. Dev Cell, 2002, 3(2): 221-231. DOI: 10.1016/S1534-5807(02)00215-0
    [24]
    LI JY, HUANG WX, ZHOU X, et al. Numb inhibits epithelial-mesenchymal transition via RBP-Jκ-dependent Notch1/PTEN/FAK signaling pathway in tongue cancer[J]. BMC Cancer, 2019, 19(1): 391. DOI: 10.1186/s12885-019-5605-5
    [25]
    ZONG FY, FU X, WEI WJ, et al. The RNA-binding protein QKI suppresses cancer-associated aberrant splicing[J]. PLoS Genet, 2014, 10(4): e1004289. DOI: 10.1371/journal.pgen.1004289
    [26]
    BECHARA EG, SEBESTYÉN E, BERNARDIS I, et al. RBM5, 6, and 10 differentially regulate Numb alternative splicing to control cancer cell proliferation[J]. Mol Cell, 2013, 52(5): 720-33. DOI: 10.1016/j.molcel.2013.11.010
    [27]
    MISQUITTA-ALI CM, CHENG E, O'HANLON D, et al. Global profiling and molecular characterization of alternative splicing events misregulated in lung cancer[J]. Mol Cell Biol, 2011, 31(1): 138-150. DOI: 10.1128/MCB.00709-10
    [28]
    KYRIAZIS GA, BELAL C, MADAN M, et al. Stress-induced switch in Numb isoforms enhances Notch-dependent expression of subtype-specific transient receptor potential channel[J]. J Biol Chem, 2010, 285(9): 6811-6825. DOI: 10.1074/jbc.M109.074690
    [29]
    SCZANIECKA M, GLADSTONE K, PETTERSSON S, et al. MDM2 protein-mediated ubiquitination of numb protein: Identification of a second physiological substrate of MDM2 that employs a dual-site docking mechanism[J]. J Biol Chem, 2012, 287(17): 14052-14068. DOI: 10.1074/jbc.M111.303875
    [30]
    NIE J, MCGILL MA, DERMER M, et al. LNX functions as a RING type E3 ubiquitin ligase that targets the cell fate determinant Numb for ubiquitin-dependent degradation[J]. EMBO J, 2002, 21(1-2): 93-102. http://www.nature.com/emboj/journal/v21/n1/abs/7594230a.html
    [31]
    NIE J, LI SS, MCGLADE CJ. A novel PTB-PDZ domain interaction mediates isoform-specific ubiquitylation of mammalian Numb[J]. J Biol Chem, 2004, 279(20): 20807-20815. DOI: 10.1074/jbc.M311396200
    [32]
    MCGILL MA, MCGLADE CJ. Mammalian numb proteins promote Notch1 receptor ubiquitination and degradation of the Notch1 intracellular domain[J]. J Biol Chem, 2003, 278(25): 23196-23203. DOI: 10.1074/jbc.M302827200
    [33]
    VOGELSTEIN B, LANE D, LEVINE AJ. Surfing the p53 network[J]. Nature, 2000, 408(6810): 307-310. DOI: 10.1038/35042675
    [34]
    YAN Z, MIAO X, ZHANG B, et al. P53 as a double-edged sword in the progression of non-alcoholic fatty liver disease[J]. Life Sci, 2018, 215: 64-72. DOI: 10.1016/j.lfs.2018.10.051
    [35]
    SONG L, CHEN TY, ZHAO XJ, et al. Pterostilbene prevents hepatocyte epithelial-mesenchymal transition in fructose-induced liver fibrosis through suppressing miR-34a/Sirt1/p53 and TGF-β1/Smads signalling[J]. Br J Pharmacol, 2019, 176(11): 1619-1634. DOI: 10.1111/bph.14573
    [36]
    YANG J, LU Y, YANG P, et al. MicroRNA-145 induces the senescence of activated hepatic stellate cells through the activation of p53 pathway by ZEB2[J]. J Cell Physiol, 2019, 234(5): 7587-7599. DOI: 10.1002/jcp.27521
    [37]
    WANG L, ZHANG Z, LI M, et al. P53-dependent induction of ferroptosis is required for artemether to alleviate carbon tetrachloride-induced liver fibrosis and hepatic stellate cell activation[J]. IUBMB Life, 2019, 71(1): 45-56. DOI: 10.1002/iub.1895
    [38]
    WENG SY, YANG CY, LI CC, et al. Synergism between p53 and Mcl-1 in protecting from hepatic injury, fibrosis and cancer[J]. J Hepatol, 2011, 54(4): 685-694. DOI: 10.1016/j.jhep.2010.07.035
    [39]
    HUANG YH, CHEN MH, GUO QL, et al. Interleukin 10 promotes primary rat hepatic stellate cell senescence by upregulating the expression levels of p53 and p21[J]. Mol Med Rep, 2018, 17(4): 5700-5707. http://www.ncbi.nlm.nih.gov/pubmed/29436649
    [40]
    COLALUCA IN, BASILE A, FREIBURGER L, et al. A Numb-Mdm2 fuzzy complex reveals an isoform-specific involvement of Numb in breast cancer[J]. J Cell Biol, 2018, 217(2): 745-762. DOI: 10.1083/jcb.201709092
    [41]
    MACHADO MV, DIEHL AM. Hedgehog signalling in liver pathophysiology[J]. J Hepatol, 2018, 68(3): 550-562. DOI: 10.1016/j.jhep.2017.10.017
    [42]
    FENG J, WANG C, LIU T, et al. Procyanidin B2 inhibits the activation of hepatic stellate cells and angiogenesis via the Hedgehog pathway during liver fibrosis[J]. J Cell Mol Med, 2019, 23(9): 6479-6493. DOI: 10.1111/jcmm.14543
    [43]
    CHUNG SI, MOON H, JU HL, et al. Hepatic expression of Sonic Hedgehog induces liver fibrosis and promotes hepatocarcinogenesis in a transgenic mouse model[J]. J Hepatol, 2016, 64(3): 618-627. DOI: 10.1016/j.jhep.2015.10.007
    [44]
    PAN XR, JING YY, LIU WT, et al. Lipopolysaccharide induces the differentiation of hepatic progenitor cells into myofibroblasts via activation of the Hedgehog signaling pathway[J]. Cell Cycle, 2017, 16(14): 1357-1365. DOI: 10.1080/15384101.2017.1325976
    [45]
    di MARCOTULLIO L, FERRETTI E, GRECO A, et al. Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination[J]. Nat Cell Biol, 2006, 8(12): 1415-1423. DOI: 10.1038/ncb1510
    [46]
    ABE Y, SUZUKI Y, KAWAMURA K, et al. MEP50/PRMT5-mediated methylation activates GLI1 in Hedgehog signalling through inhibition of ubiquitination by the ITCH/Numb complex[J]. Commun Biol, 2019, 2: 23. DOI: 10.1038/s42003-018-0275-4
    [47]
    WANG J, ZHOU T, SUN Z, et al. Zeb1 regulates the symmetric division of mouse lewis lung carcinoma stem cells through numb mediated by miR-31[J]. Int J Biol Sci, 2018, 14(11): 1399-1410. DOI: 10.7150/ijbs.27446
    [48]
    LIU WT, JING YY, GAO L, et al. Lipopolysaccharide induces the differentiation of hepatic progenitor cells into myofibroblasts constitutes the hepatocarcinogenesis-associated microenvironment[J]. Cell Death Differ, 2020, 27(1): 85-101. DOI: 10.1038/s41418-019-0340-7
    [49]
    SHEN Q, ZHONG W, JAN YN, et al. Asymmetric Numb distribution is critical for asymmetric cell division of mouse cerebral cortical stem cells and neuroblasts[J]. Development, 2002, 129(20): 4843-4853. http://europepmc.org/abstract/med/12361975
    [50]
    LU Y, XU W, JI J, et al. Alternative splicing of the cell fate determinant Numb in hepatocellular carcinoma[J]. Hepatology, 2015, 62(4): 1122-1131. DOI: 10.1002/hep.27923
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