Advertisement

Human Cell

, Volume 32, Issue 3, pp 334–342 | Cite as

The lncRNA UNC5B-AS1 promotes proliferation, migration, and invasion in papillary thyroid cancer cell lines

  • Yinghao Wang
  • Adheesh Bhandari
  • Jizhao Niu
  • Fan Yang
  • Erjie Xia
  • Zhihan Yao
  • Yixiang Jin
  • Zhouci Zheng
  • Shixu LvEmail author
  • Ouchen WangEmail author
Research Article

Abstract

The incidence of thyroid cancer detection is continually improving worldwide with the spread of diagnostic imaging and surveillance. Although we have made great progress, there are still unknown mechanisms of papillary thyroid cancer. We found that UNC5B-AS1 is a potential oncogene in thyroid cancer. Therefore, our study aimed to investigate the biological functions of the lncRNA UNC5B-AS1 in papillary thyroid cancer. As a result, RNA-seq data on primary papillary thyroid cancer (PTC) in the TCGA database were obtained. RT-qPCR was performed to evaluate the expression levels in thyroid tissue. We then analysed the expression level of UNC5B-AS1 and its association with clinicopathologic characteristics in the TCGA database. We downregulated UNC5B-AS1 using small interfering RNA and carried out assays of cell proliferation, colony formation, migration and invasion to explore the function of UNC5B-AS1 in PTC cell lines (TPC1 and BCPAP). These results suggested that the lncRNA UNC5B-AS1 was significantly upregulated in both the TCGA cohort and our tissue cohort. Upregulated UNC5B-AS1 correlated with lymph node metastasis (P < 0.001), tumor size (P = 0.002) and histological type (P = 0.013). We also achieved an area under the ROC curve (AUC) of 93.2% for our validated cohort, which was consistent with the AUC of 94.5% for the TCGA cohort, for differentiating between PTC tissues and normal tissues. Downregulating UNC5B-AS1 expression at the RNA level significantly inhibited cell proliferation, colony formation, migration, and invasion in PTC cell lines (TPC1 and BCPAP). This study demonstrated that the lncRNA UNC5B-AS1 plays an important role in tumourigenesis and metastasis of PTC and may be a potential therapeutic target for PTC.

Keywords

PTC LncRNA UNC5B-AS1 

Notes

Acknowledgements

This study was funded by the National Natural Science Foundation of China (no. 81372380).

Author contributions

AB wrote the manuscript. AB and YW did the main experiments. JN and EX collected and analysed the raw data. FY, ZY, YJ and ZZ helped to revise the article. OW and SL designed the whole work.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

This study was subject to approval by the Ethics Committee Board of the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China.

Consent for publication

Written informed consent was issued by the patients for the publication of this study. A copy of the written consent is ready for review by the Editor in Chief of this journal.

References

  1. 1.
    Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet. 2016;388(10061):2783–95.CrossRefGoogle Scholar
  2. 2.
    Schmitt AM, Chang HY. Long noncoding RNAs in cancer pathways. Cancer cell. 2016;29(4):452–63.CrossRefGoogle Scholar
  3. 3.
    Morris KV, Mattick JS. The rise of regulatory RNA. Nat Rev Genet. 2014;15(6):423–37.CrossRefGoogle Scholar
  4. 4.
    Iyer MK, Niknafs YS, Malik R, Singhal U, Sahu A, Hosono Y, et al. The landscape of long noncoding RNAs in the human transcriptome. Nat Genet. 2015;47(3):199–208.CrossRefGoogle Scholar
  5. 5.
    Banfai B, Jia H, Khatun J, Wood E, Risk B, Gundling WE Jr, et al. Long noncoding RNAs are rarely translated in two human cell lines. Genome Res. 2012;22(9):1646–57.CrossRefGoogle Scholar
  6. 6.
    Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012;81:145–66.CrossRefGoogle Scholar
  7. 7.
    Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136(4):629–41.CrossRefGoogle Scholar
  8. 8.
    Flynn RA, Chang HY. Long noncoding RNAs in cell-fate programming and reprogramming. Cell Stem Cell. 2014;14(6):752–61.CrossRefGoogle Scholar
  9. 9.
    Batista PJ, Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell. 2013;152(6):1298–307.CrossRefGoogle Scholar
  10. 10.
    Ulitsky I, Bartel DP. lincRNAs: genomics, evolution, and mechanisms. Cell. 2013;154(1):26–46.CrossRefGoogle Scholar
  11. 11.
    Geisler S, Coller J. RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts. Nat Rev Mol Cell Biol. 2013;14(11):699–712.CrossRefGoogle Scholar
  12. 12.
    Wang QX, Chen ED, Cai YF, Li Q, Jin YX, Jin WX, et al. A panel of four genes accurately differentiates benign from malignant thyroid nodules. J Exp Clin Cancer Res CR. 2016;35(1):169.CrossRefGoogle Scholar
  13. 13.
    Li J, Han L, Roebuck P, Diao L, Liu L, Yuan Y, et al. TANRIC: an interactive open platform to explore the function of lncRNAs in cancer. Cancer Res. 2015;75(18):3728–37.CrossRefGoogle Scholar
  14. 14.
    Cancer Genome Atlas Research N, Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, et al. The cancer genome atlas pan-cancer analysis project. Nat Genet. 2013;45(10):1113–20.CrossRefGoogle Scholar
  15. 15.
    Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al. The sequence of the human genome. Science. 2001;291(5507):1304–51.CrossRefGoogle Scholar
  16. 16.
    Yoon H, He H, Nagy R, Davuluri R, Suster S, Schoenberg D, et al. Identification of a novel noncoding RNA gene, NAMA, that is downregulated in papillary thyroid carcinoma with BRAF mutation and associated with growth arrest. Int J Cancer. 2007;121(4):767–75.CrossRefGoogle Scholar
  17. 17.
    Hughes CJ, Shaha AR, Shah JP, Loree TR. Impact of lymph node metastasis in differentiated carcinoma of the thyroid: a matched-pair analysis. Head Neck. 1996;18(2):127–32.CrossRefGoogle Scholar
  18. 18.
    Hwang HS, Orloff LA. Efficacy of preoperative neck ultrasound in the detection of cervical lymph node metastasis from thyroid cancer. Laryngoscope. 2011;121(3):487–91.CrossRefGoogle Scholar
  19. 19.
    Nixon IJ, Shaha AR. Management of regional nodes in thyroid cancer. Oral Oncol. 2013;49(7):671–5.CrossRefGoogle Scholar
  20. 20.
    Xing M, Alzahrani AS, Carson KA, Viola D, Elisei R, Bendlova B, et al. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA. 2013;309(14):1493–501.CrossRefGoogle Scholar
  21. 21.
    Xing M, Alzahrani AS, Carson KA, Shong YK, Kim TY, Viola D, et al. Association between BRAF V600E mutation and recurrence of papillary thyroid cancer. J Clin Oncol. 2015;33(1):42–50.CrossRefGoogle Scholar
  22. 22.
    Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011;10:38.CrossRefGoogle Scholar
  23. 23.
    Eades G, Zhang YS, Li QL, Xia JX, Yao Y, Zhou Q. Long non-coding RNAs in stem cells and cancer. World J Clin Oncol. 2014;5(2):134–41.CrossRefGoogle Scholar
  24. 24.
    Moran VA, Perera RJ, Khalil AM. Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs. Nucleic Acids Res. 2012;40(14):6391–400.CrossRefGoogle Scholar
  25. 25.
    Wang Q, Yang H, Wu L, Yao J, Meng X, Jiang H, et al. Identification of specific long non-coding RNA expression: profile and analysis of association with clinicopathologic characteristics and BRAF mutation in papillary thyroid cancer. Thyroid Off J Am Thyroid Assoc. 2016;26(12):1719–32.CrossRefGoogle Scholar
  26. 26.
    Lan X, Zhang H, Wang Z, Dong W, Sun W, Shao L, et al. Genome-wide analysis of long noncoding RNA expression profile in papillary thyroid carcinoma. Gene. 2015;569(1):109–17.CrossRefGoogle Scholar
  27. 27.
    Zhang R, Hardin H, Huang W, Chen J, Asioli S, Righi A, et al. MALAT1 long non-coding RNA expression in thyroid tissues: analysis by in situ hybridization and real-time PCR. Endocr Pathol. 2017;28(1):7–12.CrossRefGoogle Scholar
  28. 28.
    Wang Y, He H, Li W, Phay J, Shen R, Yu L, et al. MYH9 binds to lncRNA gene PTCSC2 and regulates FOXE1 in the 9q22 thyroid cancer risk locus. Proc Natl Acad Sci USA. 2017;114(3):474–9.CrossRefGoogle Scholar
  29. 29.
    Wang Y, Guo Q, Zhao Y, Chen J, Wang S, Hu J, et al. BRAF-activated long non-coding RNA contributes to cell proliferation and activates autophagy in papillary thyroid carcinoma. Oncol Lett. 2014;8(5):1947–52.CrossRefGoogle Scholar
  30. 30.
    Kong C, Zhan B, Piao C, Zhang Z, Zhu Y, Li Q. Overexpression of UNC5B in bladder cancer cells inhibits proliferation and reduces the volume of transplantation tumors in nude mice. BMC Cancer. 2016;16(1):892.CrossRefGoogle Scholar
  31. 31.
    Liu J, Kong CZ, Gong DX, Zhang Z, Zhu YY. PKC alpha regulates netrin-1/UNC5B-mediated survival pathway in bladder cancer. BMC Cancer. 2014;14:93.CrossRefGoogle Scholar
  32. 32.
    Okazaki S, Ishikawa T, Iida S, Ishiguro M, Kobayashi H, Higuchi T, et al. Clinical significance of UNC5B expression in colorectal cancer. Int J Oncol. 2012;40(1):209–16.Google Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of Thyroid and Breast SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouPeople’s Republic of China
  2. 2.Department of Cardiac SurgeryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouPeople’s Republic of China

Personalised recommendations