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Human Cell

pp 1–12 | Cite as

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

  • Xiaodong HuEmail author
  • Weiwei Liu
  • Xue Jiang
  • Bin Wang
  • Liping Li
  • Jian Wang
  • Jinhua Ma
Research Article
  • 2 Downloads

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.

Keywords

LINC00460 miR-30a-3p Rap1A Nasopharyngeal carcinoma 

Notes

Author 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.

Compliance with ethical standards

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.

Supplementary material

13577_2019_262_MOESM1_ESM.tif (41 kb)
Supplementary material 1 (TIFF 41 kb)
13577_2019_262_MOESM2_ESM.tif (40 kb)
Supplementary material 2 (TIFF 40 kb)

References

  1. 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.CrossRefGoogle Scholar
  2. 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.CrossRefGoogle Scholar
  3. 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.CrossRefGoogle Scholar
  4. 4.
    Hattori M, Minato N. Rap1 GTPase: functions, regulation, and malignancy. J Biochem. 2003;134(4):479–84.CrossRefGoogle Scholar
  5. 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.CrossRefGoogle Scholar
  6. 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.CrossRefGoogle Scholar
  7. 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.CrossRefGoogle Scholar
  8. 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.CrossRefGoogle Scholar
  9. 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.CrossRefGoogle Scholar
  10. 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.CrossRefGoogle Scholar
  11. 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.CrossRefGoogle Scholar
  12. 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.CrossRefGoogle Scholar
  13. 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.CrossRefGoogle Scholar
  14. 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.CrossRefGoogle Scholar
  15. 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.CrossRefGoogle Scholar
  16. 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.CrossRefGoogle Scholar
  17. 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.CrossRefGoogle Scholar
  18. 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.CrossRefGoogle Scholar
  19. 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.CrossRefGoogle Scholar
  20. 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.CrossRefGoogle Scholar
  21. 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.Google Scholar
  22. 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.CrossRefGoogle Scholar
  23. 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.CrossRefGoogle Scholar
  24. 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.CrossRefGoogle Scholar
  25. 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.CrossRefGoogle Scholar
  26. 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.CrossRefGoogle Scholar
  27. 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.CrossRefGoogle Scholar

Copyright information

© Japan Human Cell Society and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  • Xiaodong Hu
    • 1
    Email author
  • Weiwei Liu
    • 1
  • Xue Jiang
    • 1
  • Bin Wang
    • 1
  • Liping Li
    • 1
  • Jian Wang
    • 1
  • Jinhua Ma
    • 1
  1. 1.E.N.T. DepartmentCangzhou Central HospitalCangzhouPeople’s Republic of China

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