Volume 19 Issue 2
Feb.  2021
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Article Navigation >  Chinese Journal of General Practice  > 2021  >  19(2): 182-185, 269
WANG Qiang-hua, PANG Qing, WANG Xue-gu, WU Hua, CHEN Hui-juan, ZHAO Wen-jun, LI Xiang. The role of PI3K/ Akt signaling pathway in upregulation of ISG15 induced by interferon 2α in hepatocellular carcinoma cells[J]. Chinese Journal of General Practice, 2021, 19(2): 182-185, 269. doi: 10.16766/j.cnki.issn.1674-4152.001762
Citation: WANG Qiang-hua, PANG Qing, WANG Xue-gu, WU Hua, CHEN Hui-juan, ZHAO Wen-jun, LI Xiang. The role of PI3K/ Akt signaling pathway in upregulation of ISG15 induced by interferon 2α in hepatocellular carcinoma cells[J]. Chinese Journal of General Practice, 2021, 19(2): 182-185, 269. doi: 10.16766/j.cnki.issn.1674-4152.001762
shu

The role of PI3K/ Akt signaling pathway in upregulation of ISG15 induced by interferon 2α in hepatocellular carcinoma cells

doi: 10.16766/j.cnki.issn.1674-4152.001762
  • 1.

    Department of Infectious Diseases, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China

Funds:

 2008085J37

 BYKY18111

  • Received Date: 2020-10-16
    Available Online: 2022-02-19
    Abstract
  •   Objective  To investigate the mechanism of protein expression of interferon-stimulated gene 15 (ISG15) induced by interferon 2α (IFN-2α) via phosphatidy linositol 3-kinase (PI3K)/protein kinase B (Akt) in hepatocellular carcinoma cells.  Methods  HepG2 cells were cultured in the media containing IFN-2α and/or PI3K inhibitor LY294002, and four groups were created: control, IFN-2α, LY294002, IFN-2α+LY294002. The protein expressions of Akt, p-Akt and ISG15 were determined using western blot. Immunofluorescence was used to determine the co-expression of p-Akt and ISG15. Data were analyzed with one-way ANOVA followed by Bonferroni post hoc tests.  Results  Western blot analysis showed that the protein expression of ISG 15 was significantly increased in the IFN-2α group compared with control and IFN-2α+LY294002 group. Immunostaining analysis showed that the fluorescence intensity of ISG15 in the IFN-2α group was significantly higher than that in control and IFN-2α+LY294002 group. Western blot analysis showed that, in the IFN-2α group, the level of p-Akt (Thr308) was significantly increased, while the p-Akt (Ser473) was significantly decreased, compared with control group. Immunofluorescence results showed that the fluorescence intensity of p-Akt (Thr308) in the IFN-2α group was significantly higher than that in the control group and the IFN-2α+LY294002 group.  Conclusion  In HepG2 cells, IFN-2α induces the protein expression of ISG 15 via increasing p-Akt (Thr308) in the PI3K/Akt pathway.

     

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    • References(19)
  • [1]
    MAK L Y, CRUZ-RAMÓN V, CHINCHILLA-LÓPEZ P, et al. Global epidemiology, prevention, and management of hepatocellular carcinoma[J]. Am Soc Clin Oncol Educ Book, 2018, 38: 262-279. http://www.onacademic.com/detail/journal_1000042310209299_1fc0.html
    [2]
    BORDEN E C. Interferons alpha and beta in cancer: therapeutic opportunities from new insights[J]. Nat Rev Drug Discov, 2019, 18(3): 219-234. doi: 10.1038/s41573-018-0011-2
    [3]
    MARTIN-HIJANO L, SAINZ B J R. The interactions between cancer stem cells and the innate interferon signaling pathway[J]. Front Immunol, 2020, 11: 526. doi: 10.3389/fimmu.2020.00526
    [4]
    ZHOU S, REN M, XU H, et al. Inhibition of ISG15 enhances the anti-cancer effect of trametinib in colon cancer cells[J]. Onco Targets Ther, 2019, 12: 10239-10250. doi: 10.2147/OTT.S226395
    [5]
    YAN X, LIU X P, GUO Z X, et al. Identification of hub genes associated with progression and prognosis in patients with bladder cancer[J]. Front Genet, 2019, 10: 408. doi: 10.3389/fgene.2019.00408
    [6]
    TECALCO-CRUZ A C, CORTÉS-GONZÁLEZ C C, CRUZ-RAMOS E, et al. Interplay between interferon-stimulated gene 15/ISGylation and interferon gamma signaling in breast cancer cells[J]. Cell Signal, 2019, 54: 91-101. doi: 10.1016/j.cellsig.2018.11.021
    [7]
    GAO Y, YANG J, CAI Y, et al. IFN-gamma-mediated inhibition of lung cancer correlates with PD-L1 expression and is regulated by PI3K-AKT signaling[J]. Int J Cancer, 2018, 143(4): 931-943. doi: 10.1002/ijc.31357
    [8]
    YEH Y H, HSIAO H F, YEH Y C, et al. Inflammatory interferon activates HIF-1alpha-mediated epithelial-to-mesenchymal transition via PI3K/AKT/mTOR pathway[J]. J Exp Clin Cancer Res, 2018, 37(1): 70. doi: 10.1186/s13046-018-0730-6
    [9]
    CHANDRASHEKAR D S, BASHEL B, BALASUBRAMANYA S A H, et al. UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses[J]. Neoplasia, 2017, 19(8): 649-658. doi: 10.1016/j.neo.2017.05.002
    [10]
    ZHU Y, SONG D, SONG Y, et al. Interferon gamma induces inflammatory responses through the interaction of CEACAM1 and PI3K in airway epithelial cells[J]. J Transl Med, 2019, 17(1): 147. doi: 10.1186/s12967-019-1894-3
    [11]
    WAN X X, CHEN H C, KHAN M A, et al. ISG15 inhibits IFN-alpha-resistant liver cancer cell growth[J]. Biomed Res Int, 2013, 2013: 570909. http://europepmc.org/abstract/med/24024201
    [12]
    SCHNEIDER W M, CHEVILLOTTE M D, RICE C M. Interferon-stimulated genes: a complex web of host defenses[J]. Annu Rev Immunol, 2014, 32: 513-545. doi: 10.1146/annurev-immunol-032713-120231
    [13]
    ZHANG Y, LI X, ZHANG Y, et al. Pegylated interferon-alpha inhibits the proliferation of hepatocellular carcinoma cells by downregulating miR-155[J]. Ann Hepatol, 2019, 18(3): 494-500. doi: 10.1016/j.aohep.2018.11.007
    [14]
    SPROOTEN J, AGOSTINIS P, GARG A D. Type I interferons and dendritic cells in cancer immunotherapy[J]. Int Rev Cell Mol Biol, 2019, 348: 217-262. http://www.sciencedirect.com/science/article/pii/S1937644819300620
    [15]
    CHEN R H, DU Y, HAN P, et al. ISG15 predicts poor prognosis and promotes cancer stem cell phenotype in nasopharyngeal carcinoma[J]. Oncotarget, 2016, 7(13): 16910-16922. doi: 10.18632/oncotarget.7626
    [16]
    KAUR S, SASSANO A, DOLNIAK B, et al. Role of the Akt pathway in mRNA translation of interferon-stimulated genes[J]. Proc Natl Acad Sci U S A, 2008, 105(12): 4808-4813. doi: 10.1073/pnas.0710907105
    [17]
    TIAN J, ZHANG X, WU H, et al. Blocking the PI3K/AKT pathway enhances mammalian reovirus replication by repressing IFN-stimulated genes[J]. Front Microbiol, 2015, 6: 886. http://pdfs.semanticscholar.org/a087/143ccafb8699cca687a6548e99633a98fe21.pdf
    [18]
    LEI H, FURLONG P J, RA J H, et al. AKT activation and response to interferon-beta in human cancer cells[J]. Cancer Biol Ther, 2005, 4(7): 709-715. doi: 10.4161/cbt.4.7.1767
    [19]
    VINCENT E E, ELDER D J, THOMAS E C, et al. Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer[J]. Br J Cancer, 2011, 104(11): 1755-1761. doi: 10.1038/bjc.2011.132
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