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.
PTC LncRNA UNC5B-AS1
This is a preview of subscription content, log in to check access.
This study was funded by the National Natural Science Foundation of China (no. 81372380).
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.
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
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
Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012;81:145–66.CrossRefGoogle Scholar
Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136(4):629–41.CrossRefGoogle Scholar
Flynn RA, Chang HY. Long noncoding RNAs in cell-fate programming and reprogramming. Cell Stem Cell. 2014;14(6):752–61.CrossRefGoogle Scholar
Batista PJ, Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell. 2013;152(6):1298–307.CrossRefGoogle Scholar
Ulitsky I, Bartel DP. lincRNAs: genomics, evolution, and mechanisms. Cell. 2013;154(1):26–46.CrossRefGoogle Scholar
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
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
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
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
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
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
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
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
Nixon IJ, Shaha AR. Management of regional nodes in thyroid cancer. Oral Oncol. 2013;49(7):671–5.CrossRefGoogle Scholar
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
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
Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011;10:38.CrossRefGoogle Scholar
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
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
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
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
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
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
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
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
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
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