Skip to main content
SpringerLink
Log in

Long noncoding RNA LINC00460 aggravates invasion and metastasis by targeting miR-30a-3p/Rap1A in nasopharyngeal carcinoma

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Accumulating studies have shown that long noncoding RNAs (lncRNAs) are involved in cancer occurrence and development. Recently a new lncRNA LINC00460 has been reported to be upregulated in several types of cancers. In this study, we investigated the role of LINC00460 in invasion and metastasis of nasopharyngeal carcinoma (NPC). In NPC cell lines named C666-1 and 5-8F, LINC00460 overexpression promoted cancer cell migration, invasion and epithelial-mesenchymal transition (EMT), while depletion of LINC00460 exhibited opposite effects. We further demonstrated that LINC00460 regulated Rap1A expression through competitively binding to miR-30a-3p. LINC00460 knockdown suppressed NPC metastasis in a xenograft mouse model. Taken together, our findings suggested LINC00460 functioned as an oncogene in NPC which promoted invasion and metastasis, shedding lights on LINC00460 as a potential therapeutic target for NPC therapeutics from bench to clinic.

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
Fig. 7

Similar content being viewed by others

References

  1. Chua MLK, Wee JTS, Hui EP, Chan ATC. Nasopharyngeal carcinoma. Lancet. 2016;387(10022):1012–24. https://doi.org/10.1016/S0140-6736(15)00055-0.

    Article  PubMed  Google Scholar 

  2. Colaco RJ, Betts G, Donne A, Swindell R, Yap BK, Sykes AJ, et al. Nasopharyngeal carcinoma: a retrospective review of demographics, treatment and patient outcome in a single centre. Clin Oncol. 2013;25(3):171–7. https://doi.org/10.1016/j.clon.2012.10.006.

    Article  CAS  Google Scholar 

  3. Lee AW, Ng WT, Chan YH, Sze H, Chan C, Lam TH. The battle against nasopharyngeal cancer. Radiother Oncol J Eur Soc Ther Radiol Oncol. 2012;104(3):272–8. https://doi.org/10.1016/j.radonc.2012.08.001.

    Article  Google Scholar 

  4. Hattori M, Minato N. Rap1 GTPase: functions, regulation, and malignancy. J Biochem. 2003;134(4):479–84.

    Article  CAS  Google Scholar 

  5. Pizon V, Baldacci G. Rap1A protein interferes with various MAP kinase activating pathways in skeletal myogenic cells. Oncogene. 2000;19(52):6074–81. https://doi.org/10.1038/sj.onc.1203984.

    Article  CAS  PubMed  Google Scholar 

  6. Bos JL. Linking Rap to cell adhesion. Curr Opin Cell Biol. 2005;17(2):123–8. https://doi.org/10.1016/j.ceb.2005.02.009.

    Article  CAS  PubMed  Google Scholar 

  7. Bailey CL, Kelly P, Casey PJ. Activation of Rap1 promotes prostate cancer metastasis. Can Res. 2009;69(12):4962–8. https://doi.org/10.1158/0008-5472.CAN-08-4269.

    Article  CAS  Google Scholar 

  8. Xiang J, Bian C, Wang H, Huang S, Wu D. MiR-203 down-regulates Rap1A and suppresses cell proliferation, adhesion and invasion in prostate cancer. J Exp Clin Cancer Res CR. 2015;34:8. https://doi.org/10.1186/s13046-015-0125-x.

    Article  CAS  PubMed  Google Scholar 

  9. Wang K, Li J, Guo H, Xu X, Xiong G, Guan X, et al. MiR-196a binding-site SNP regulates RAP1A expression contributing to esophageal squamous cell carcinoma risk and metastasis. Carcinogenesis. 2012;33(11):2147–54. https://doi.org/10.1093/carcin/bgs259.

    Article  CAS  PubMed  Google Scholar 

  10. Huang M, Anand S, Murphy EA, Desgrosellier JS, Stupack DG, Shattil SJ, et al. EGFR-dependent pancreatic carcinoma cell metastasis through Rap1 activation. Oncogene. 2012;31(22):2783–93. https://doi.org/10.1038/onc.2011.450.

    Article  CAS  PubMed  Google Scholar 

  11. Lu L, Wang J, Wu Y, Wan P, Yang G. Rap1A promotes ovarian cancer metastasis via activation of ERK/p38 and notch signaling. Cancer Med. 2016;5(12):3544–54. https://doi.org/10.1002/cam4.946.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011;43(6):904–14. https://doi.org/10.1016/j.molcel.2011.08.018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hauptman N, Glavac D. Long non-coding RNA in cancer. Int J Mol Sci. 2013;14(3):4655–69. https://doi.org/10.3390/ijms14034655.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bhan A, Soleimani M, Mandal SS. Long noncoding RNA and cancer: a new paradigm. Can Res. 2017;77(15):3965–81. https://doi.org/10.1158/0008-5472.CAN-16-2634.

    Article  CAS  Google Scholar 

  15. He R, Hu Z, Wang Q, Luo W, Li J, Duan L, et al. The role of long non-coding RNAs in nasopharyngeal carcinoma: as systemic review. Oncotarget. 2017;8(9):16075–83. https://doi.org/10.18632/oncotarget.14211.

    Article  PubMed  Google Scholar 

  16. Lian Y, Yan C, Xu H, Yang J, Yu Y, Zhou J, et al. A novel lncRNA, LINC00460, affects cell proliferation and apoptosis by regulating KLF2 and CUL4A expression in colorectal cancer. Mol Ther Nucleic Acids. 2018;12:684–97. https://doi.org/10.1016/j.omtn.2018.06.012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wang X, Mo FM, Bo H, Xiao L, Chen GY, Zeng PW, et al. Upregulated expression of long non-coding RNA, LINC00460, suppresses proliferation of colorectal cancer. J Cancer. 2018;9(16):2834–43. https://doi.org/10.7150/jca.26046.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wang F, Liang S, Liu X, Han L, Wang J, Du Q. LINC00460 modulates KDM2A to promote cell proliferation and migration by targeting miR-342-3p in gastric cancer. OncoTargets Ther. 2018;11:6383–94. https://doi.org/10.2147/OTT.S169307.

    Article  Google Scholar 

  19. Li K, Sun D, Gou Q, Ke X, Gong Y, Zuo Y, et al. Long non-coding RNA linc00460 promotes epithelial-mesenchymal transition and cell migration in lung cancer cells. Cancer Lett. 2018;420:80–90. https://doi.org/10.1016/j.canlet.2018.01.060.

    Article  CAS  PubMed  Google Scholar 

  20. Kong YG, Cui M, Chen SM, Xu Y, Xu Y, Tao ZZ. LncRNA-LINC00460 facilitates nasopharyngeal carcinoma tumorigenesis through sponging miR-149-5p to up-regulate IL6. Gene. 2018;639:77–84. https://doi.org/10.1016/j.gene.2017.10.006.

    Article  CAS  PubMed  Google Scholar 

  21. Liz J, Esteller M. lncRNAs and microRNAs with a role in cancer development. Biochem Biophys Acta. 2016;1859(1):169–76. https://doi.org/10.1016/j.bbagrm.2015.06.015.

    Article  CAS  PubMed  Google Scholar 

  22. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–33. https://doi.org/10.1016/j.cell.2009.01.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Liu Z, Luo W, Zhou Y, Zhen Y, Yang H, Yu X, et al. Potential tumor suppressor NESG1 as an unfavorable prognosis factor in nasopharyngeal carcinoma. PLoS ONE. 2011;6(11):e27887. https://doi.org/10.1371/journal.pone.0027887.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hu C, Wei W, Chen X, Woodman CB, Yao Y, Nicholls JM, et al. A global view of the oncogenic landscape in nasopharyngeal carcinoma: an integrated analysis at the genetic and expression levels. PLoS ONE. 2012;7(7):e41055. https://doi.org/10.1371/journal.pone.0041055.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Tsuji T, Ibaragi S, Hu GF. Epithelial-mesenchymal transition and cell cooperativity in metastasis. Can Res. 2009;69(18):7135–9. https://doi.org/10.1158/0008-5472.CAN-09-1618.

    Article  CAS  Google Scholar 

  26. Martin MD, Matrisian LM. The other side of MMPs: protective roles in tumor progression. Cancer Metastasis Rev. 2007;26(3–4):717–24. https://doi.org/10.1007/s10555-007-9089-4.

    Article  CAS  PubMed  Google Scholar 

  27. Kumarswamy R, Mudduluru G, Ceppi P, Muppala S, Kozlowski M, Niklinski J, et al. MicroRNA-30a inhibits epithelial-to-mesenchymal transition by targeting Snai1 and is downregulated in non-small cell lung cancer. Int J Cancer. 2012;130(9):2044–53. https://doi.org/10.1002/ijc.26218.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. E.N.T. Department, Cangzhou Central Hospital, Comprehensive Building of Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou Canal District, Cangzhou, 061000, Hebei, People’s Republic of China

    Xiaodong Hu, Weiwei Liu, Xue Jiang, Bin Wang, Liping Li, Jian Wang & Jinhua Ma

Authors
  1. Xiaodong Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weiwei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xue Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Liping Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jian Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jinhua Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XDH and WWL conceived and designed the experiments, XL and BW analyzed and interpreted the results of the experiments, LPL, JW and JHM performed the experiments.

Corresponding author

Correspondence to Xiaodong Hu.

Ethics declarations

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Informed consent

Written informed consent was obtained from a legally authorized representative(s) for anonymized patient information to be published in this article.

Conflict of interest

Authors declared that there were no conflicts of interests.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Ethical approval regarding animal study was granted from the Animal Ethics Committee of Cangzhou Central Hospital. Ethical consent was granted from the Medical Ethics Committee of Cangzhou Central Hospital for study involving patients.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (TIFF 41 kb)

Supplementary material 2 (TIFF 40 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hu, X., Liu, W., Jiang, X. et al. Long noncoding RNA LINC00460 aggravates invasion and metastasis by targeting miR-30a-3p/Rap1A in nasopharyngeal carcinoma. Human Cell 32, 465–476 (2019). https://doi.org/10.1007/s13577-019-00262-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-019-00262-4

Keywords

Search

Navigation