Skip to main content

Advertisement

SpringerLink
Log in

Upregulated expression of ILF2 in non-small cell lung cancer is associated with tumor cell proliferation and poor prognosis

  • Original Paper
  • Published:
Journal of Molecular Histology Aims and scope Submit manuscript

Abstract

ILF2 (NF45) is a sequence-specific DNA binding protein that is involved in mitosis control, transcriptional regulation, DNA breaks repair, microRNA processing and viral replication. In the present study, we aim to investigate the potential role of ILF2 in the progression of non–small cell lung cancer (NSCLC). Western blot analysis indicated that ILF2 was up-regulated in NSCLC tissues, compared with adjacent non-tumorous ones. Furthermore, immunohistochemistry analysis showed that the expression of ILF2 was correlated with histological differentiation, clinical stage and Ki-67 expression in NSCLC specimens. In addition, using Kaplan–Meier survival analysis, we found that high expression of ILF2 predicted poor outcome in NSCLC patients. Furthermore, we showed that up-regulated expression of ILF2 might play a regulatory role in the proliferation of NSCLC cells using serum starvation and release assay. Moreover, knockdown of ILF2 inhibited cell proliferation and cell cycle progress of NSCLC cells. In conclusion, our results indicated that ILF2 was involved in the pathogenesis of NSCLC and might be a potential target for NSCLC therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Aaboe M, Marcussen N, Jensen KM, Thykjaer T, Dyrskjot L, Orntoft TF (2005) Gene expression profiling of noninvasive primary urothelial tumours using microarrays. Br J Cancer 93:1182–1190

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Barber GN (2009) The NFAR’s (nuclear factors associated with dsRNA): evolutionarily conserved members of the dsRNA binding protein family. RNA Biol 6:35–39

    Article  CAS  PubMed  Google Scholar 

  • Cai J et al (2013) miR-205 targets PTEN and PHLPP2 to augment AKT signaling and drive malignant phenotypes in non-small cell lung cancer. Cancer Res 73:5402–5415

    Article  CAS  PubMed  Google Scholar 

  • Chung FH, Lee HH, Lee HC (2013) ToP: a trend-of-disease-progression procedure works well for identifying cancer genes from multi-state cohort gene expression data for human colorectal cancer. PLoS One 8:e65683

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • DeGregori J, Kowalik T, Nevins JR (1995) Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes. Mol Cell Biol 15:4215–4224

    PubMed Central  CAS  PubMed  Google Scholar 

  • Faye MD, Graber TE, Liu P, Thakor N, Baird SD, Durie D, Holcik M (2013) Nucleotide composition of cellular internal ribosome entry sites defines dependence on NF45 and predicts a posttranscriptional mitotic regulon. Mol Cell Biol 33:307–318

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fung LF, Lo AK, Yuen PW, Liu Y, Wang XH, Tsao SW (2000) Differential gene expression in nasopharyngeal carcinoma cells. Life Sci 67:923–936

    Article  CAS  PubMed  Google Scholar 

  • Guan D et al (2008) Nuclear factor 45 (NF45) is a regulatory subunit of complexes with NF90/110 involved in mitotic control. Mol Cell Biol 28:4629–4641

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Guo NL et al (2008) Confirmation of gene expression-based prediction of survival in non-small cell lung cancer. Clin Cancer Res 14:8213–8220

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Guo Y et al (2012) Correlations among ERCC1, XPB, UBE2I, EGF, TAL2 and ILF3 revealed by gene signatures of histological subtypes of patients with epithelial ovarian cancer. Oncol Rep 27:286–292

    CAS  PubMed  Google Scholar 

  • Hu Q et al (2013) Interleukin enhancer-binding factor 3 promotes breast tumor progression by regulating sustained urokinase-type plasminogen activator expression. Oncogene 32:3933–3943

    Article  CAS  PubMed  Google Scholar 

  • Hu B, Mu HP, Zhang YQ, Su CY, Song JT, Meng C, Liu DX (2014) Prognostic significance of TBX2 expression in non-small cell lung cancer. J Mol Histol 45:421–426

    Article  CAS  PubMed  Google Scholar 

  • Huang Q et al (2014) Expression of NF45 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth. Tumour Biol 35:10149–10157

    Article  CAS  PubMed  Google Scholar 

  • Janku F, Stewart DJ, Kurzrock R (2010) Targeted therapy in non-small-cell lung cancer–is it becoming a reality? Nat Rev Clin Oncol 7:401–414

    Article  CAS  PubMed  Google Scholar 

  • Ji L et al (2014) Transformer 2beta (Tra2beta/SFRS10) positively regulates the progression of NSCLC via promoting cell proliferation. J Mol Histol 45:573–582

    Article  CAS  PubMed  Google Scholar 

  • Jiang W et al (2014) Regulation of cell cycle of hepatocellular carcinoma by NF90 through modulation of cyclin E1 mRNA stability. Oncogene. doi:10.1038/onc.2014.373

  • Kao PN, Chen L, Brock G, Ng J, Kenny J, Smith AJ, Corthesy B (1994) Cloning and expression of cyclosporin A- and FK506-sensitive nuclear factor of activated T-cells: NF45 and NF90. J Biol Chem 269:20691–20699

    CAS  PubMed  Google Scholar 

  • Kim IM et al (2006) The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer. Cancer Res 66:2153–2161

    Article  CAS  PubMed  Google Scholar 

  • Kuzuhara T, Suganuma M, Kurusu M, Fujiki H (2007) Helicobacter pylori-secreting protein Tipalpha is a potent inducer of chemokine gene expressions in stomach cancer cells. J Cancer Res Clin Oncol 133:287–296

    Article  CAS  PubMed  Google Scholar 

  • Lee YY et al (2011) Subcellular tissue proteomics of hepatocellular carcinoma for molecular signature discovery. J Proteome Res 10:5070–5083

    Article  CAS  PubMed  Google Scholar 

  • Li W et al (2013) TRAF4 is a critical molecule for Akt activation in lung cancer. Cancer Res 73:6938–6950

    Article  CAS  PubMed  Google Scholar 

  • Liu Y et al (2013) Vacuolar protein sorting 4B, an ATPase protein positively regulates the progression of NSCLC via promoting cell division. Mol Cell Biochem 381:163–171

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Fernandez LA, Parraga M, del Mazo J (2002) Ilf2 is regulated during meiosis and associated to transcriptionally active chromatin. Mech Dev 111:153–157

    Article  CAS  PubMed  Google Scholar 

  • Ni S et al (2015) Expression and clinical role of NF45 as a novel cell cycle protein in esophageal squamous cell carcinoma (ESCC). Tumour Biol 36:747–756

    Article  CAS  PubMed  Google Scholar 

  • Osada H, Takahashi T (2002) Genetic alterations of multiple tumor suppressors and oncogenes in the carcinogenesis and progression of lung cancer. Oncogene 21:7421–7434

    Article  CAS  PubMed  Google Scholar 

  • Sakamoto S et al (2009) The NF90–NF45 complex functions as a negative regulator in the microRNA processing pathway. Mol Cell Biol 29:3754–3769

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shamanna RA, Hoque M, Lewis-Antes A, Azzam EI, Lagunoff D, Pe’ery T, Mathews MB (2011) The NF90/NF45 complex participates in DNA break repair via nonhomologous end joining. Mol Cell Biol 31:4832–4843

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shim C, Zhang W, Rhee CH, Lee JH (1998) Profiling of differentially expressed genes in human primary cervical cancer by complementary DNA expression array. Clin Cancer Res 4:3045–3050

    CAS  PubMed  Google Scholar 

  • Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30

    Article  PubMed  Google Scholar 

  • Stricker RL, Behrens SE, Mundt E (2010) Nuclear factor NF45 interacts with viral proteins of infectious bursal disease virus and inhibits viral replication. J Virol 84:10592–10605

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Takamizawa J et al (2004) Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64:3753–3756

    Article  CAS  PubMed  Google Scholar 

  • Vumbaca F, Phoenix KN, Rodriguez-Pinto D, Han DK, Claffey KP (2008) Double-stranded RNA-binding protein regulates vascular endothelial growth factor mRNA stability, translation, and breast cancer angiogenesis. Mol Cell Biol 28:772–783

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wang HJ, Shao JZ, Xiang LX, Shen J (2006) Molecular cloning, characterization and expression analysis of an ILF2 homologue from Tetraodon nigroviridis. J Biochem Mol Biol 39:686–695

    Article  CAS  PubMed  Google Scholar 

  • Wang Y et al (2013) Interaction with cyclin H/cyclin-dependent kinase 7 (CCNH/CDK7) stabilizes C-terminal binding protein 2 (CtBP2) and promotes cancer cell migration. J Biol Chem 288:9028–9034

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wang J et al (2014) The reverse effect of X-ray irradiation on acquired gefitinib resistance in non-small cell lung cancer cell line NCI-H1975 in vitro. J Mol Histol 45:641–652

    Article  CAS  PubMed  Google Scholar 

  • Wood SL, Pernemalm M, Crosbie PA, Whetton AD (2014) The role of the tumor-microenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets. Cancer Treat Rev 40:558–566

    Article  CAS  PubMed  Google Scholar 

  • Zhang T, Zhang DM, Zhao D, Hou XM, Liu XJ, Ling XL, Ma SC (2014) The prognostic value of osteopontin expression in non-small cell lung cancer: a meta-analysis. J Mol Histol 45:533–540

    Article  CAS  PubMed  Google Scholar 

  • Zhao G, Shi L, Qiu D, Hu H, Kao PN (2005) NF45/ILF2 tissue expression, promoter analysis, and interleukin-2 transactivating function. Exp Cell Res 305:312–323

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Supported by Grants from the National Natural Science Foundation of China (No. 81201858); Natural Scientific Foundation of Jiangsu Province Grant (No. BK2012231).

Conflict of interest

The authors declare no conflict of interest.

Author information

Author notes

    Authors and Affiliations

    1. Department of Oncology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China

      Tingting Ni, Guoxin Mao, Buyou Chen & Liting Lv

    2. Department of Pathology, Medical College, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu Province, China

      Yifei Liu, Yuchan Wang & Lili Ji

    3. Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China

      Qun Xue

    4. Department of Respiratory Diseases, First Affiliated Hospital, Nanjing Medical University, Nanjing, 210029, China

      Xuefan Cui & Liangliang Jia

    Authors
    1. Tingting Ni
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Guoxin Mao
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Qun Xue
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Yifei Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Buyou Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Xuefan Cui
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Liting Lv
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Liangliang Jia
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Yuchan Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Lili Ji
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Yuchan Wang or Lili Ji.

    Additional information

    Tingting Ni and Guoxin Mao have contributed equally to this study.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Ni, T., Mao, G., Xue, Q. et al. Upregulated expression of ILF2 in non-small cell lung cancer is associated with tumor cell proliferation and poor prognosis. J Mol Hist 46, 325–335 (2015). https://doi.org/10.1007/s10735-015-9624-5

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10735-015-9624-5

    Keywords

    Search

    Navigation