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Overexpression of Rsf-1 correlates with poor survival and promotes invasion in non-small cell lung cancer

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Abstract

Rsf-1 (HBXAP) was recently reported to play roles in tumorigenesis and tumor progression. There have been many reports referred to Rsf-1 overexpression in various cancers and associated with the malignant behavior of cancer cells. However, the molecular mechanism of Rsf-1 in non-small cell lung cancer aggressiveness remains ambiguous. In the present study, we found that there was a significant association between Rsf-1 overexpression and poor overall survival (p = 0.028) in lung cancer. Furthermore, knockdown of Rsf-1 expression in H1299 and H460 cells with high endogenous Rsf-1 expression inhibited cell migration and invasion and downregulated MMP2 expression and nuclear levels of NF-κB. NF-κB inhibitor could also block the effect of Rsf-1 in regulation of MMP2 expression. Further experiments demonstrated that Rsf-1 depletion restrained NF-κB reporter luciferase activity and downregulated bcl-2 and p-IκB protein level. In conclusion, we demonstrated that Rsf-1 was overexpressed in lung cancer and associated with poor survival. Rsf-1 regulated cell invasion through MMP2 and NF-κB pathway.

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Reference

  1. Shih IM, Sheu JJ, Santillan A, Nakayama K, Yen MJ, Bristow RE, Vang R, Parmigiani G, Kurman RJ, Trope CG, Davidson B, Wang TL (2005) Amplification of a chromatin remodeling gene, Rsf-1/HBXAP, in ovarian carcinoma. Proc Natl Acad Sci U S A 102:14004–14009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Davidson B, Trope’ CG, Wang TL, Shih IM (2006) Expression of the chromatin remodeling factor Rsf-1 is upregulated in ovarian carcinoma effusions and predicts poor survival. Gynecol Oncol 103:814–819

    Article  CAS  PubMed  Google Scholar 

  3. Mao TL, Hsu CY, Yen MJ, Gilks B, Sheu JJ, Gabrielson E, Vang R, Cope L, Kurman RJ, Wang TL, Shih IM (2006) Expression of Rsf-1, a chromatin-remodeling gene, in ovarian and breast carcinoma. Hum Pathol 37:1169–1175

    Article  CAS  PubMed  Google Scholar 

  4. Fang FM, Li CF, Huang HY, Lai MT, Chen CM, Chiu IW, Wang TL, Tsai FJ, Shih IM, Sheu JJ (2011) Overexpression of a chromatin remodeling factor, RSF-1/HBXAP, correlates with aggressive oral squamous cell carcinoma. Am J Pathol 178:2407–2415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Schwab M (1998) Amplification of oncogenes in human cancer cells. BioEssays 20:473–479

    Article  CAS  PubMed  Google Scholar 

  6. Tai HC, Huang HY, Lee SW, Lin CY, Sheu MJ, Chang SL, Wu LC, Shiue YL, Wu WR, Lin CM, Li CF (2012) Associations of Rsf-1 overexpression with poor therapeutic response and worse survival in patients with nasopharyngeal carcinoma. J Clin Pathol 65:248–253

    Article  PubMed  Google Scholar 

  7. Xu J, Tyan T, Cedrone E, Savaraj N (1996) Wang N. Detection of 11q13 amplification as the origin of a homogeneously staining region in small cell lung cancer by chromosome microdissection. Genes Chromosomes Cancer 17:172–178

    Article  CAS  PubMed  Google Scholar 

  8. Shibata T, Uryu S, Kokubu A, Hosoda F, Ohki M, Sakiyama T, Matsuno Y, Tsuchiya R, Kanai Y, Kondo T, Imoto I, Inazawa J, Hirohashi S (2005) Genetic classification of lung adenocarcinoma based on array-based comparative genomic hybridization analysis: its association with clinicopathologic features. Clin Cancer Res 11:6177–6185

    Article  CAS  PubMed  Google Scholar 

  9. Brown LA, Irving J, Parker R, Kim H, Press JZ, Longacre TA, Chia S, Magliocco A, Makretsov N, Gilks B, Pollack J, Huntsman D (2006) Amplification of EMSY, a novel oncogene on 11q13, in high grade ovarian surface epithelial carcinomas. Gynecol Oncol 100:264–270

    Article  CAS  PubMed  Google Scholar 

  10. Hennessy BT, Nanjundan M, Cheng KW, Nolden L, Mills GB (2006) Identification of remodeling and spacing factor 1 (Rsf-1, HBXAP) at chromosome 11q13 as a putative oncogene in ovarian cancer. Eur J Hum Genet 14:381–383

    Article  CAS  PubMed  Google Scholar 

  11. Bostner J, Ahnström Waltersson M, Fornander T, Skoog L, Nordenskjöld B, Stål O (2007) Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer. Oncogene 26:6997–7005

    Article  CAS  PubMed  Google Scholar 

  12. Rosen A, Sevelda P, Klein M, Dobianer K, Hruza C, Czerwenka K, Hanak H, Vavra N, Salzer H, Leodolter S (1993) First experience with FGF-3 (INT-2) amplification in women with epithelial ovarian cancer. Br J Cancer 67:1122–1125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Cheng CK, Chow LW, Loo WT, Chan TK, Chan V (2005) The cell cycle checkpoint gene Rad9 is a novel oncogene activated by 11q13 amplification and DNA methylation in breast cancer. Cancer Res 65:8646–8654

    Article  CAS  PubMed  Google Scholar 

  14. Jezierska A, Motyl T (2009) Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review. Med Sci Monit 15:RA32–RA40

    CAS  PubMed  Google Scholar 

  15. Tokuraku M, Sato H, Murakami S, Okada Y, Watanabe Y, Seiki M (1995) Activation of the precursor of gelatinase A/72 kDa type IV collagenase/MMP-2 in lung carcinomas correlates with the expression of membrane-type matrix metalloproteinase (MT-MMP) and with lymph node metastasis. Int J Cancer 64:355–359

    Article  CAS  PubMed  Google Scholar 

  16. Kenny HA, Kaur S, Coussens LM, Lengyel E (2008) The initial steps of ovarian cancer cell metastasis are mediated by MMP-2 cleavage of vitronectin and fibronectin. J Clin Invest 118:1367–1379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Guttridge DC, Albanese C, Reuther JY, Pestell RG, Baldwin AS Jr (1999) NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol Cell Biol 19:5785–5799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chen C, Edelstein LC, Gélinas C (2000) The Rel/NF-kappaB family directly activates expression of the apoptosis inhibitor Bcl-x(L). Mol Cell Biol 20:2687–2695

    Article  PubMed  PubMed Central  Google Scholar 

  19. Fernández-Majada V, Aguilera C, Villanueva A, Vilardell F, Robert-Moreno A, Aytés A, Real FX, Capella G, Mayo MW, Espinosa L, Bigas A (2007) Nuclear IKK activity leads to dysregulated notch-dependent gene expression in colorectal cancer. Proc Natl Acad Sci U S A 104:276–281

    Article  PubMed  Google Scholar 

  20. Tew GW, Lorimer EL, Berg TJ, Zhi H, Li R, Williams CL (2008) SmgGDS regulates cell proliferation, migration, and NF-kappaB transcriptional activity in non-small cell lung carcinoma. J Biol Chem 283:963–976

    Article  CAS  PubMed  Google Scholar 

  21. Rahman KM, Ali S, Aboukameel A, Sarkar SH, Wang Z, Philip PA, Sakr WA, Raz A (2007) Inactivation of NF-kappaB by 3,3′-diindolylmethane contributes to increased apoptosis induced by chemotherapeutic agent in breast cancer cells. Mol Cancer Ther 6:2757–2765

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, The 1st Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, 110001, People’s Republic of China

    Xiuwei Zhang, Lin Fu, Xiupeng Zhang, Fengxia Hao, Lingling Xie, Jiani He, Junda Gai, Yuhui Liu, Hongtao Xu, Qingchang Li & Enhua Wang

  2. Department of Pathology, The 4th Affiliated Hospital of China Medical University, Shenyang, 110032, China

    Xiuwei Zhang

  3. Department of Urology, The 4th Affiliated Hospital of China Medical University, Shenyang, 110032, China

    Dongwei Xue

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  1. Xiuwei Zhang
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  2. Lin Fu
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  3. Dongwei Xue
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  4. Xiupeng Zhang
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  5. Fengxia Hao
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  6. Lingling Xie
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  7. Jiani He
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  9. Yuhui Liu
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  10. Hongtao Xu
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  11. Qingchang Li
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  12. Enhua Wang
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Corresponding author

Correspondence to Qingchang Li.

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The study protocol was approved by the institutional reviewer board of China Medical University. All participants provided written informed consent, and the investigation was conducted according to the principles expressed in the Declaration of Helsinki.

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The authors declare that they have no conflict of interest.

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Zhang, X., Fu, L., Xue, D. et al. Overexpression of Rsf-1 correlates with poor survival and promotes invasion in non-small cell lung cancer. Virchows Arch 470, 553–560 (2017). https://doi.org/10.1007/s00428-017-2102-6

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  • DOI: https://doi.org/10.1007/s00428-017-2102-6

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