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01-04-2020 | Thyroid Cancer | Original Article

Molecular Network-Based Identification of Circular RNA-Associated ceRNA Network in Papillary Thyroid Cancer

Authors: Qin Liu, Liang-zhi Pan, Min Hu, Jian-ying Ma

Published in: Pathology & Oncology Research | Issue 2/2020

Abstract

Circular RNAs (circRNAs) have displayed dysregulated expression in several types of cancer. Nevertheless, their function and underlying mechanisms in papillary thyroid cancer (PTC) remains largely unknown. This study aimed to describe the regulatory mechanisms in PTC. The expression profile of circRNA was download from the Gene Expression Omnibus (GEO) database. The mRNA and miRNA data of PTC was downloaded from The Cancer Genome Atlas (TCGA) database. The circRNA-miRNA-mRNA network by Cytoscape. The interactions between proteins were analyzed using the STRING database and hubgenes were identified using MCODE plugin. Then, we conducted a circRNA-miRNA-hubgenes regulatory module. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis were conducted using R packages “Clusterprofile”. We identified 14 differential expression circRNAs (DEcircRNA), 3106 differential expression mRNAs (DEmRNA), 142 differential expression miRNAs (DEmiRNA) and in PTC. Twelve circRNAs, 33 miRNAs, and 356 mRNAs were identified to construct the ceRNA network of PTC. PPI network and module analysis identified 5 hubgenes. Then, a circRNA-miRNA-hubgene subnetwork was constructed based on the 2 DEcircRNAs, 3 DEmiRNAs, and 4 DEmRNAs. GO and KEGG pathway analysis indicated DEmRNAs might be associated with PTC onset and progression. These ceRNAs are critical in the pathogenesis of PTC and may serve as future therapeutic biomarkers.

Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68(1):7–30. https://doi.org/10.3322/caac.21442 CrossRefPubMed

Mao Y, Xing M (2016) Recent incidences and differential trends of thyroid cancer in the USA. Endocr Relat Cancer 23(4):313–322. https://doi.org/10.1530/erc-15-0445 CrossRefPubMedPubMedCentral

Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L (2016) 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid Cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid Cancer. Thyroid. 26(1):1–133. https://doi.org/10.1089/thy.2015.0020 CrossRefPubMedPubMedCentral

Liu FH, Kuo SF, Hsueh C, Chao TC, Lin JD (2015) Postoperative recurrence of papillary thyroid carcinoma with lymph node metastasis. J Surg Oncol 112(2):149–154. https://doi.org/10.1002/jso.23967 CrossRefPubMedPubMedCentral

Grant CS (2015) Recurrence of papillary thyroid cancer after optimized surgery. Gland Surg 4(1):52–62. https://doi.org/10.3978/j.issn.2227-684X.2014.12.06 CrossRefPubMedPubMedCentral

Qu S, Yang X, Li X, Wang J, Gao Y, Shang R, Sun W, Dou K, Li H (2015) Circular RNA: a new star of noncoding RNAs. Cancer Lett 365(2):141–148. https://doi.org/10.1016/j.canlet.2015.06.003 CrossRefPubMed

Chen LL (2016) The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol 17(4):205–211. https://doi.org/10.1038/nrm.2015.32 CrossRefPubMed

Wang F, Nazarali AJ, Ji S (2016) Circular RNAs as potential biomarkers for cancer diagnosis and therapy. Am J Cancer Res 6(6):1167–1176PubMedPubMedCentral

Li J, Yang J, Zhou P, le Y, Zhou C, Wang S, Xu D, Lin HK, Gong Z (2015) Circular RNAs in cancer: novel insights into origins, properties, functions and implications. Am J Cancer Res 5(2):472–480PubMedPubMedCentral

10.

Liu M, Liu KD, Zhang L et al (2018) Circ_0009910 regulates growth and metastasis and is associated with poor prognosis in gastric cancer. J Cell Biochem 22(23):8248–8256. https://doi.org/10.26355/eurrev_201812_16519 CrossRef

11.

Zhang X, Xu Y, Qian Z et al (2018) circRNA_104075 stimulates YAP-dependent tumorigenesis through the regulation of HNF4a and may serve as a diagnostic marker in hepatocellular carcinoma. Cell Death Dis 9(11):1091. https://doi.org/10.1038/s41419-018-1132-6 CrossRefPubMedPubMedCentral

12.

Zhang G, Sun W, Zhu L, Feng Y, Wu L, Li T (2018) Overexpressed circ_0029426 in glioblastoma forecasts unfavorable prognosis and promotes cell progression by sponging miR-197. J Cell Biochem 120:10295–10302. https://doi.org/10.1002/jcb.28313 CrossRefPubMed

13.

Liu G, Huang K, Jie Z, Wu Y, Chen J, Chen Z, Fang X, Shen S (2018) CircFAT1 sponges miR-375 to promote the expression of yes-associated protein 1 in osteosarcoma cells. Mol Cancer 17(1):170. https://doi.org/10.1186/s12943-018-0917-7 CrossRefPubMedPubMedCentral

14.

Li X, Zhang Z, Jiang H, Li Q, Wang R, Pan H, Niu Y, Liu F, Gu H, Fan X, Gao J (2018) Circular RNA circPVT1 promotes proliferation and invasion through sponging miR-125b and activating E2F2 signaling in non-small cell lung Cancer. J Cell Biochem 51(5):2324–2340. https://doi.org/10.1159/000495876 CrossRef

15.

Wang R, Zhang S, Chen X et al (2018) EIF4A3-induced circular RNA MMP9 (circMMP9) acts as a sponge of miR-124 and promotes glioblastoma multiforme cell tumorigenesis. 17(1):166. https://doi.org/10.1186/s12943-018-0911-0

16.

Wong N, Wang X (2015) miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res 43(Database issue):D146–D152. https://doi.org/10.1093/nar/gku1104 CrossRefPubMed

17.

Fromm B, Billipp T, Peck LE, Johansen M, Tarver JE, King BL, Newcomb JM, Sempere LF, Flatmark K, Hovig E, Peterson KJ (2015) A uniform system for the annotation of vertebrate microRNA genes and the evolution of the human microRNAome. Annu Rev Genet 49:213–242. https://doi.org/10.1146/annurev-genet-120213-092023 CrossRefPubMedPubMedCentral

18.

Yu G, Wang LG, Han Y, He QY (2012) clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 16(5):284–287. https://doi.org/10.1089/omi.2011.0118 CrossRefPubMedPubMedCentral

19.

Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, Marzluff WF, Sharpless NE (2013) Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 19(2):141–157. https://doi.org/10.1261/rna.035667.112 CrossRefPubMedPubMedCentral

20.

Rybak-Wolf A, Stottmeister C, Glazar P et al (2015) Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed. Mol Cell 58(5):870–885. https://doi.org/10.1016/j.molcel.2015.03.027 CrossRefPubMed

21.

Lux S, Bullinger L (2018) Circular RNAs in Cancer. Adv Exp Med Biol 1087:215–230. https://doi.org/10.1007/978-981-13-1426-1_17 CrossRefPubMed

22.

Chen S, Zhao Y (2018) Circular RNAs: characteristics, function, and role in human cancer. Histol Histopathol 33(9):887–893. https://doi.org/10.14670/hh-11-969 CrossRefPubMed

23.

Kristensen LS, Hansen TB, Veno MT, Kjems J (2018) Circular RNAs in cancer: opportunities and challenges in the field. Oncogene. 37(5):555–565. https://doi.org/10.1038/onc.2017.361 CrossRefPubMed

24.

Zhong Y, Du Y, Yang X et al (2018) Circular RNAs function as ceRNAs to regulate and control human cancer progression. Mol Cancer 17(1):79. https://doi.org/10.1186/s12943-018-0827-8 CrossRefPubMedPubMedCentral

25.

Chen F, Feng Z, Zhu J, Liu P, Yang C, Huang R, Deng Z (2018) Emerging roles of circRNA_NEK6 targeting miR-370-3p in the proliferation and invasion of thyroid cancer via Wnt signaling pathway. Cancer Biol Ther 19(12):1139–1152. https://doi.org/10.1080/15384047.2018.1480888 CrossRefPubMedPubMedCentral

26.

Wei H, Pan L, Tao D, Li R (2018) Circular RNA circZFR contributes to papillary thyroid cancer cell proliferation and invasion by sponging miR-1261 and facilitating C8orf4 expression. Biochem Biophys Res Commun 503(1):56–61. https://doi.org/10.1016/j.bbrc.2018.05.174 CrossRefPubMed

27.

Liu F, Zhang J, Qin L et al (2018) Circular RNA EIF6 (Hsa_circ_0060060) sponges miR-144-3p to promote the cisplatin-resistance of human thyroid carcinoma cells by autophagy regulation. Aging (Albany NY) 10(12):3806–3820. https://doi.org/10.18632/aging.101674 CrossRef

28.

Jin X, Wang Z, Pang W et al (2018) Upregulated hsa_circ_0004458 contributes to progression of papillary thyroid carcinoma by inhibition of miR-885-5p and activation of RAC1. Med Sci Monit 24:5488–5500. https://doi.org/10.12659/msm.911095 CrossRefPubMedPubMedCentral

29.

Jiang W, Wen D, Gong L, Wang Y, Liu Z, Yin F (2018) Circular RNA hsa_circ_0000673 promotes hepatocellular carcinoma malignance by decreasing miR-767-3p targeting SET. Biochem Biophys Res Commun 500(2):211–216. https://doi.org/10.1016/j.bbrc.2018.04.041 CrossRefPubMed

30.

Chang P, Wang F, Li Y (2018) Hsa_circ_0000673 is down-regulated in gastric cancer and inhibits the proliferation and invasion of tumor cells by targetting miR-532-5p. Biosci Rep 38(5). https://doi.org/10.1042/bsr20180538

31.

Bartel DP (2018) Metazoan MicroRNAs. Cell. 173(1):20–51. https://doi.org/10.1016/j.cell.2018.03.006 CrossRefPubMedPubMedCentral

32.

Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell. 136(2):215–233. https://doi.org/10.1016/j.cell.2009.01.002 CrossRefPubMedPubMedCentral

33.

Liu C, Liu R, Zhang D, Deng Q, Liu B, Chao HP, Rycaj K, Takata Y, Lin K, Lu Y, Zhong Y, Krolewski J, Shen J, Tang DG (2017) MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes. Nat Commun 8:14270CrossRefPubMedPubMedCentral

34.

Song HM, Luo Y, Li DF, Wei CK, Hua KY, Song JL, Xu H, Maskey N, Fang L (2015) MicroRNA-96 plays an oncogenic role by targeting FOXO1 and regulating AKT/FOXO1/Bim pathway in papillary thyroid carcinoma cells. Int J Clin Exp Pathol 8(9):9889–9900PubMedPubMedCentral

35.

Spitschak A, Meier C, Kowtharapu B, Engelmann D, Putzer BM (2017) MiR-182 promotes cancer invasion by linking RET oncogene activated NF-kappaB to loss of the HES1/Notch1 regulatory circuit. Mol Cancer 16(1):24. https://doi.org/10.1186/s12943-016-0563-x CrossRefPubMedPubMedCentral

36.

Wu ZY, Wang SM, Chen ZH, Huv SX, Huang K, Huang BJ, du JL, Huang CM, Peng L, Jian ZX, Zhao G (2015) MiR-204 regulates HMGA2 expression and inhibits cell proliferation in human thyroid cancer. Cancer Biomark 15(5):535–542. https://doi.org/10.3233/cbm-150492 CrossRefPubMed

37.

Li J, Zheng X, Gao M, Zhao J, Li Y, Meng X, Qian B, Li J (2017) Suberoyl bis-hydroxamic acid activates Notch1 signaling and induces apoptosis in anaplastic thyroid carcinoma through p53. Oncol Rep 37(1):458–464. https://doi.org/10.3892/or.2016.5281 CrossRefPubMed

38.

Kim YH, Choi YW, Lee J, Soh EY, Kim JH, Park TJ (2017) Senescent tumor cells lead the collective invasion in thyroid cancer. Nat Commun 8:15208. https://doi.org/10.1038/ncomms15208 CrossRefPubMedPubMedCentral

Title: Molecular Network-Based Identification of Circular RNA-Associated ceRNA Network in Papillary Thyroid Cancer
Authors: Qin Liu
Liang-zhi Pan
Min Hu
Jian-ying Ma
Publication date: 01-04-2020
Publisher: Springer Netherlands
Keywords: Thyroid Cancer
Thyroid Cancer
Thyroid Cancer
Published in: Pathology & Oncology Research / Issue 2/2020
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-019-00697-y

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