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Interferon regulatory factor 4 (IRF4) is overexpressed in human non‑small cell lung cancer (NSCLC) and activates the Notch signaling pathway

  • Authors:
    • Yajuan Qian
    • Ziyan Du
    • Yufei Xing
    • Tong Zhou
    • Ting Chen
    • Minhua Shi
  • View Affiliations / Copyright

    Affiliations: Department of Respiration, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
    Copyright: © Qian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 6034-6040
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    Published online on: August 22, 2017
       https://doi.org/10.3892/mmr.2017.7319
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Abstract

The transcription factor, interferon regulatory factor 4 (IRF4), serves an essential role in the regulation of immune responses, and has been reported to act as a diagnostic and prognostic marker for various hematological malignancies. The present study aimed to investigate whether IRF4 could exert effects on human non‑small cell lung cancer (NSCLC) and to explore the underlying mechanism. The mRNA and protein expression of IRF4 was detected in NSCLC tissues using reverse‑transcription quantitative polymerase chain reaction and western blotting, respectively. In the in vitro experiment, IRF4 expression was knocked down or overexpressed using lentivirus in human lung adenocarcinoma A549 and lung squamous cell carcinoma LC‑AI cell lines. Cell proliferation and colony number were analyzed using MTT and colony formation assays, respectively. The expression levels of IRF4 mRNA and protein were significantly higher in NSCLC tissues (n=54) compared with that in adjacent non‑tumor tissues. Similarly, the expression levels of Notch1 and Notch2 mRNA were significantly higher in NSCLC tissues. Furthermore, the expression level of IRF4 mRNA was positively correlated with the levels of Notch1 and Notch2 mRNA in NSCLC tissues. Consequently, using NSCLC cell lines, it was demonstrated that the knockdown of IRF4 expression significantly reduced the cell proliferation rate and colony formation, whereas IRF4‑overexpression significantly increased them. Notably, the IRF4 knockdown significantly decreased the expression levels of Notch1 and Notch2 mRNA, and phosphorylated protein kinase B (AKT), whereas IRF4 overexpression resulted in the opposite. The results of the present study indicate that IRF4 is overexpressed and serves as a tumor promoter in human NSCLC, at least partially, through activating the Notch‑Akt signaling pathway.
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1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Yuan X, Wu H, Han N, Xu H, Chu Q, Yu S, Chen Y and Wu K: Notch signaling and EMT in non-small cell lung cancer: Biological significance and therapeutic application. J Hematol Oncol. 7:872014. View Article : Google Scholar : PubMed/NCBI

3 

Baumgart A, Mazur P, Anton M, Rudelius M, Schwamborn K, Feuchtinger A, Behnke K, Walch A, Braren R, Peschel C, et al: Opposing role of Notch1 and Notch2 in a Kras(G12D)-driven murine non-small cell lung cancer model. Oncogene. 34:578–588. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Coffelt SB, Hughes R and Lewis CE: Tumor-associated macrophages: Effectors of angiogenesis and tumor progression. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 1796:11–18. 2009. View Article : Google Scholar

5 

Honda K and Taniguchi T: IRFs: Master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol. 6:644–658. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Mamane Y, Heylbroeck C, Génin P, Algarté M, Servant MJ, LePage C, DeLuca C, Kwon H, Lin R and Hiscott J: Interferon regulatory factors: The next generation. Gene. 237:1–14. 1999. View Article : Google Scholar : PubMed/NCBI

7 

Taniguchi T, Ogasawara K, Takaoka A and Tanaka N: IRF family of transcription factors as regulators of host defense. Annual Rev immunol. 19:623–655. 2001. View Article : Google Scholar

8 

Wang L and Ning S: Interferon regulatory factor 4 is activated through c-Src-mediated tyrosine phosphorylation in virus-transformed cells. J Virol. 87:9672–9679. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Spender LC, Lucchesi W, Bodelon G, Bilancio A, Karstegl CE, Asano T, Dittrich-Breiholz O, Kracht M, Vanhaesebroeck B and Farrell PJ: Cell target genes of Epstein-Barr virus transcription factor EBNA-2: Induction of the p55alpha regulatory subunit of PI3-kinase and its role in survival of EREB2. 5 cells. J Gen Virol. 87:2859–2867. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Iida S, Rao PH, Butler M, Corradini P, Boccadoro M, Klein B, Chaganti RS and Dalla-Favera R: Deregulation of MUM1/IRF4 by chromosomal translocation in multiple myeloma. Nat Genet. 17:226–230. 1997. View Article : Google Scholar : PubMed/NCBI

11 

Mamane Y, Grandvaux N, Hernandez E, Sharma S, Innocente SA, Lee JM, Azimi N, Lin R and Hiscott J: Repression of IRF-4 target genes in human T cell leukemia virus-1 infection. Oncogene. 21:6751–6765. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Sharma S, Mamane Y, Grandvaux N, Bartlett J, Petropoulos L, Lin R and Hiscott J: Activation and regulation of interferon regulatory factor 4 in HTLV type 1-infected T lymphocytes. AIDS Res Hum Retroviruses. 16:1613–1622. 2000. View Article : Google Scholar : PubMed/NCBI

13 

Ortmann CA, Burchert A, Hölzle K, Nitsche A, Wittig B, Neubauer A and Schmidt M: Down-regulation of interferon regulatory factor 4 gene expression in leukemic cells due to hypermethylation of CpG motifs in the promoter region. Nucleic Acids Res. 33:6895–6905. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Schmidt M, Hochhaus A, König-Merediz SA, Brendel C, Proba J, Hoppe GJ, Wittig B, Ehninger G, Hehlmann R and Neubauer A: Expression of interferon regulatory factor 4 in chronic myeloid leukemia: Correlation with response to interferon alfa therapy. J Clin Oncol. 18:3331–3338. 2000. View Article : Google Scholar : PubMed/NCBI

15 

Tsuboi K, Iida S, Inagaki H, Kato M, Hayami Y, Hanamura I, Miura K, Harada S, Kikuchi M, Komatsu H, et al: MUM 1/IRF4 expression as a frequent event in mature lymphoid malignancies. Leukemia. 14:449–456. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Yang M, Yuan F, Li P, Chen Z, Chen A, Li S and Hu C: Interferon regulatory factor 4 binding protein is a novel p53 target gene and suppresses cisplatin-induced apoptosis of breast cancer cells. Mol Cancer. 11:542012. View Article : Google Scholar : PubMed/NCBI

17 

Chen HY, Yu SL, Chen CH, Chang GC, Chen CY, Yuan A, Cheng CL, Wang CH, Terng HJ, Kao SF, et al: A five-gene signature and clinical outcome in non-small-cell lung cancer. N Engl J Med. 356:11–20. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Blackman SC, Podtelezhnikov A, Railkar RA, Loboda A, Tanis K, Klappenbach JA, Watters J, Iannone R, Herman G and Bergtrom DA: Abstract 26: Notch pathway inhibition with MK-0752 leads to dose- and time-dependent transcriptional alterations in proliferation, PI3K, and Wnt pathway genes in plucked human hair follicles. Cancer Res. 70:17–21. 2010. View Article : Google Scholar

19 

Zhao J and Lever AM: Lentivirus-mediated gene expression. Methods Mol Biol. 366:343–355. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Harper JA, Yuan JS, Tan JB, Visan I and Guidos CJ: Notch signaling in development and disease. Clin Genet. 64:461–472. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Kadesch T: Notch signaling: The demise of elegant simplicity. Curr Opin Genet Dev. 14:506–512. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Ellisen LW, Bird J, West DC, Soreng AL, Reynolds TC, Smith SD and Sklar J: TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell. 66:649–661. 1991. View Article : Google Scholar : PubMed/NCBI

23 

Shukla V, Shukla A, Joshi SS and Lu R: Interferon regulatory factor 4 attenuates Notch signaling to suppress the development of chronic lymphocytic leukemia. Oncotarget. 7:41081–41094. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Zhu H, Bhaijee F, Ishaq N, Pepper DJ, Backus K, Brown AS, Zhou X and Miele L: Correlation of Notch1, pAKT and nuclear NF-κB expression in triple negative breast cancer. Am J Cancer Res. 3:230–239. 2013.PubMed/NCBI

25 

Gualco G, Weiss LM and Bacchi CE: MUM1/IRF4: A Review. Appl Immunohistochem Mol Morphol. 18:301–310. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Wu YY, Hwang YT, Perng WC, Chian CF, Ho CL, Lee SC, Chang H, Terng HJ and Chao TY: CPEB4 and IRF4 expression in peripheral mononuclear cells are potential prognostic factors for advanced lung cancer. J Formos Med Assoc. 116:114–122. 2017. View Article : Google Scholar : PubMed/NCBI

27 

Artavanis-Tsakonas S, Rand MD and Lake RJ: Notch signaling: Cell fate control and signal integration in development. Science. 284:770–776. 1999. View Article : Google Scholar : PubMed/NCBI

28 

Bray SJ: Notch signalling: A simple pathway becomes complex. Nat Rev Mol Cell Biol. 7:678–689. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Weijzen S, Rizzo P, Braid M, Vaishnav R, Jonkheer SM, Zlobin A, Osborne BA, Gottipati S, Aster JC, Hahn WC, et al: Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells. Nat Med. 8:979–986. 2002. View Article : Google Scholar : PubMed/NCBI

30 

Allen TD, Rodriguez EM, Jones KD and Bishop JM: Activated Notch1 induces lung adenomas in mice and cooperates with Myc in the generation of lung adenocarcinoma. Cancer Res. 71:6010–6018. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Osanyingbemi-Obidi J, Dobromilskaya I, Illei PB, Hann CL and Rudin CM: Notch signaling contributes to lung cancer clonogenic capacity in vitro but may be circumvented in tumorigenesis in vivo. Mol Cancer Res. 9:1746–1754. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Baumgart A, Seidl S, Vlachou P, Michel L, Mitova N, Schatz N, Specht K, Koch I, Schuster T, Grundler R, et al: ADAM17 regulates epidermal growth factor receptor expression through the activation of Notch1 in non-small cell lung cancer. Cancer Res. 70:5368–5378. 2010. View Article : Google Scholar : PubMed/NCBI

33 

Mimae T, Okada M, Hagiyama M, Miyata Y, Tsutani Y, Inoue T, Murakami Y and Ito A: Upregulation of notch2 and six1 is associated with progression of early-stage lung adenocarcinoma and a more aggressive phenotype at advanced stages. Clin Cancer Res. 18:945–955. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Fan X, Mikolaenko I, Elhassan I, Ni X, Wang Y, Ball D, Brat DJ, Perry A and Eberhart CG: Notch1 and notch2 have opposite effects on embryonal brain tumor growth. Cancer Res. 64:7787–7793. 2004. View Article : Google Scholar : PubMed/NCBI

35 

Graziani I, Eliasz S, De Marco MA, Chen Y, Pass HI, De May RM, Strack PR, Miele L and Bocchetta M: Opposite effects of Notch-1 and Notch-2 on mesothelioma cell survival under hypoxia are exerted through the Akt pathway. Cancer Res. 68:9678–9685. 2008. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Qian Y, Du Z, Xing Y, Zhou T, Chen T and Shi M: Interferon regulatory factor 4 (IRF4) is overexpressed in human non‑small cell lung cancer (NSCLC) and activates the Notch signaling pathway. Mol Med Rep 16: 6034-6040, 2017.
APA
Qian, Y., Du, Z., Xing, Y., Zhou, T., Chen, T., & Shi, M. (2017). Interferon regulatory factor 4 (IRF4) is overexpressed in human non‑small cell lung cancer (NSCLC) and activates the Notch signaling pathway. Molecular Medicine Reports, 16, 6034-6040. https://doi.org/10.3892/mmr.2017.7319
MLA
Qian, Y., Du, Z., Xing, Y., Zhou, T., Chen, T., Shi, M."Interferon regulatory factor 4 (IRF4) is overexpressed in human non‑small cell lung cancer (NSCLC) and activates the Notch signaling pathway". Molecular Medicine Reports 16.5 (2017): 6034-6040.
Chicago
Qian, Y., Du, Z., Xing, Y., Zhou, T., Chen, T., Shi, M."Interferon regulatory factor 4 (IRF4) is overexpressed in human non‑small cell lung cancer (NSCLC) and activates the Notch signaling pathway". Molecular Medicine Reports 16, no. 5 (2017): 6034-6040. https://doi.org/10.3892/mmr.2017.7319
Copy and paste a formatted citation
x
Spandidos Publications style
Qian Y, Du Z, Xing Y, Zhou T, Chen T and Shi M: Interferon regulatory factor 4 (IRF4) is overexpressed in human non‑small cell lung cancer (NSCLC) and activates the Notch signaling pathway. Mol Med Rep 16: 6034-6040, 2017.
APA
Qian, Y., Du, Z., Xing, Y., Zhou, T., Chen, T., & Shi, M. (2017). Interferon regulatory factor 4 (IRF4) is overexpressed in human non‑small cell lung cancer (NSCLC) and activates the Notch signaling pathway. Molecular Medicine Reports, 16, 6034-6040. https://doi.org/10.3892/mmr.2017.7319
MLA
Qian, Y., Du, Z., Xing, Y., Zhou, T., Chen, T., Shi, M."Interferon regulatory factor 4 (IRF4) is overexpressed in human non‑small cell lung cancer (NSCLC) and activates the Notch signaling pathway". Molecular Medicine Reports 16.5 (2017): 6034-6040.
Chicago
Qian, Y., Du, Z., Xing, Y., Zhou, T., Chen, T., Shi, M."Interferon regulatory factor 4 (IRF4) is overexpressed in human non‑small cell lung cancer (NSCLC) and activates the Notch signaling pathway". Molecular Medicine Reports 16, no. 5 (2017): 6034-6040. https://doi.org/10.3892/mmr.2017.7319
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