CircRNAs: A Novel Strategy in Diagnosis and Treatment of Thyroid
Cancer

Rana      Shafabakhsh; Zatollah      Asemi; Mohammad   Ali   Mansournia; Bahman      Yousefi; Jamal      Hallajzadeh
Abstract

Thyroid cancer is one of the most frequent cancers globally, and its incidence has risen recently. The clinical behavior of thyroid cancer includes a wide range, from benign to invasive malignant tumors. Thus, precious diagnostic activities before therapeutic work are required. Circular RNAs (circRNAs) along with microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are known as non-coding RNAs (ncRNAs). Large amounts of investigations have indicated that circRNAs can participate in multiple cellular processes, especially in tumorigenesis. Furthermore, circRNAs are stable in blood or plasma, as well as they are specific in different tissues. Therefore, they could serve as a potential diagnostic biomarker for cancer cells. Limited studies investigated the role of circRNAs in some processes involved in thyroid cancer. In this review, we summarized the current evidence on the potential clinical involvement of circRNAs in thyroid cancer.
Keywords: CircRNAs, apoptosis, microRNA, signaling pathway, thyroid cancer, neuroendocrine cell.
[1]
Durante C, Costante G, Lucisano G, et al. The natural history of benign thyroid nodules. JAMA  2015; 313(9): 926-35.
 [http://dx.doi.org/10.1001/jama.2015.0956] [PMID: 25734734]

[2]
Dralle H, Machens A, Basa J, et al. Follicular cell-derived thyroid cancer. Nat Rev Dis Primers  2015; 1: 15077.
 [http://dx.doi.org/10.1038/nrdp.2015.77] [PMID: 27188261]

[3]
Caron NR, Clark OH. Papillary thyroid cancer. Curr Treat Options Oncol  2006; 7(4): 309-19.
 [http://dx.doi.org/10.1007/s11864-006-0040-7] [PMID: 16916491]

[4]
Grimm D. Current knowledge in thyroid cancer-from bench to bedside. Int J Mol Sci  2017; 18(7): E1529.
 [http://dx.doi.org/10.3390/ijms18071529] [PMID: 28714875]

[5]
Shah JP. Thyroid carcinoma: Epidemiology, histology, and diagnosis. Clin Adv Hematol Oncol  2015; 13(4 Suppl): 3-6.

[6]
Cote GJ, Grubbs EG, Hofmann MC. Thyroid C-cell biology and oncogenic transformation. Recent Results Cancer Res  2015; 204: 1-39.
 [http://dx.doi.org/10.1007/978-3-319-22542-5_1] [PMID: 26494382]

[7]
Wells SA Jr, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid  2015; 25(6): 567-610.
 [http://dx.doi.org/10.1089/thy.2014.0335]

[8]
Moley JF. Medullary thyroid carcinoma: Management of lymph node metastases. J Natl Compr Canc Netw  2010; 8(5): 549-56.
 [http://dx.doi.org/10.6004/jnccn.2010.0042] [PMID: 20495084]

[9]
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell  2011; 144(5): 646-74.
 [http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]

[10]
Raman P, Koenig RJ. Pax-8-PPAR-γ fusion protein in thyroid carcinoma. Nat Rev Endocrinol  2014; 10(10): 616-23.
 [http://dx.doi.org/10.1038/nrendo.2014.115] [PMID: 25069464]

[11]
Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol  2011; 7(10): 569-80.
 [http://dx.doi.org/10.1038/nrendo.2011.142] [PMID: 21878896]

[12]
Molinaro E, Romei C, Biagini A, et al. Anaplastic thyroid carcinoma: From clinicopathology to genetics and advanced therapies. Nat Rev Endocrinol  2017; 13(11): 644-60.
 [http://dx.doi.org/10.1038/nrendo.2017.76] [PMID: 28707679]

[13]
Smolle E, Haybaeck J. Non-coding RNAs and lipid metabolism. Int J Mol Sci  2014; 15(8): 13494-513.
 [http://dx.doi.org/10.3390/ijms150813494] [PMID: 25093715]

[14]
Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature  2013; 495(7441): 333-8.
 [http://dx.doi.org/10.1038/nature11928] [PMID: 23446348]

[15]
Lambertini M, Santoro L, Del Mastro L, et al. Reproductive behaviors and risk of developing breast cancer according to tumor subtype: A systematic review and meta-analysis of epidemiological studies. Cancer Treat Rev  2016; 49: 65-76.
 [http://dx.doi.org/10.1016/j.ctrv.2016.07.006] [PMID: 27529149]

[16]
Bach DH, Lee SK, Sood AK. Circular RNAs in Cancer. Mol Ther Nucleic Acids  2019; 16: 118-29.
 [http://dx.doi.org/10.1016/j.omtn.2019.02.005] [PMID: 30861414]

[17]
Song L, Xiao Y. Downregulation of hsa_circ_0007534 suppresses breast cancer cell proliferation and invasion by targeting miR-593/MUC19 signal pathway. Biochem Biophys Res Commun  2018; 503(4): 2603-10.
 [http://dx.doi.org/10.1016/j.bbrc.2018.08.007] [PMID: 30139516]

[18]
Chen G, Wang Q, Yang Q, et al. Circular RNAs hsa_circ_0032462, hsa_circ_0028173, hsa_circ_0005909 are predicted to promote CADM1 expression by functioning as miRNAs sponge in human osteosarcoma. PLoS One  2018; 13(8): e0202896.

[19]
Wang L, Wei Y, Yan Y, et al. CircDOCK1 suppresses cell apoptosis via inhibition of miR-196a-5p by targeting BIRC3 in OSCC. Oncol Rep  2018; 39(3): 951-66.
 [PMID: 29286141]

[20]
Yin Y, Long J, He Q, et al. Emerging roles of circRNA in formation and progression of cancer. J Cancer  2019; 10(21): 5015-21.
 [http://dx.doi.org/10.7150/jca.30828] [PMID: 31602252]

[21]
Pan H, Li T, Jiang Y, et al. Overexpression of circular RNA ciRS-7 abrogates the tumor suppressive effect of miR-7 on gastric cancer via PTEN/PI3K/AKT signaling pathway. J Cell Biochem  2018; 119(1): 440-6.
 [http://dx.doi.org/10.1002/jcb.26201] [PMID: 28608528]

[22]
Memczak S, Papavasileiou P, Peters O, Rajewsky N. Identification and characterization of circular RNAs as a new class of putative biomarkers in human blood. PLoS One  2015; 10(10): e0141214.
 [http://dx.doi.org/10.1371/journal.pone.0141214] [PMID: 26485708]

[23]
Cocquerelle C, Mascrez B, Hétuin D, Bailleul B. Mis-splicing yields circular RNA molecules. FASEB J  1993; 7(1): 155-60.
 [http://dx.doi.org/10.1096/fasebj.7.1.7678559] [PMID: 7678559]

[24]
Chen I, Chen CY, Chuang TJ. Biogenesis, identification, and function of exonic circular RNAs. Wiley Interdiscip Rev RNA  2015; 6(5): 563-79.
 [http://dx.doi.org/10.1002/wrna.1294] [PMID: 26230526]

[25]
Westholm JO, Miura P, Olson S, et al. Genome-wide analysis of drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation. Cell Rep  2014; 9(5): 1966-80.
 [http://dx.doi.org/10.1016/j.celrep.2014.10.062] [PMID: 25544350]

[26]
Zhang XO, Dong R, Zhang Y, et al. Diverse alternative back-splicing and alternative splicing landscape of circular RNAs. Genome Res  2016; 26(9): 1277-87.
 [http://dx.doi.org/10.1101/gr.202895.115] [PMID: 27365365]

[27]
Jeck WR, Sorrentino JA, Wang K, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA  2013; 19(2): 141-57.
 [http://dx.doi.org/10.1261/rna.035667.112] [PMID: 23249747]

[28]
Zhang Y, Zhang XO, Chen T, et al. Circular intronic long noncoding RNAs. Mol Cell  2013; 51(6): 792-806.
 [http://dx.doi.org/10.1016/j.molcel.2013.08.017] [PMID: 24035497]

[29]
Li Z, Huang C, Bao C, et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol  2015; 22(3): 256-64.
 [http://dx.doi.org/10.1038/nsmb.2959] [PMID: 25664725]

[30]
Lu Z, Filonov GS, Noto JJ, et al. Metazoan tRNA introns generate stable circular RNAs in vivo. RNA  2015; 21(9): 1554-65.
 [http://dx.doi.org/10.1261/rna.052944.115] [PMID: 26194134]

[31]
Kohlhapp FJ, Mitra AK, Lengyel E, Peter ME. MicroRNAs as mediators and communicators between cancer cells and the tumor microenvironment. Oncogene  2015; 34(48): 5857-68.
 [http://dx.doi.org/10.1038/onc.2015.89] [PMID: 25867073]

[32]
Hansen TB, Jensen TI, Clausen BH, et al. Natural RNA circles function as efficient microRNA sponges. Nature  2013; 495(7441): 384-8.
 [http://dx.doi.org/10.1038/nature11993] [PMID: 23446346]

[33]
Guo JU, Agarwal V, Guo H, Bartel DP. Expanded identification and characterization of mammalian circular RNAs. Genome Biol  2014; 15(7): 409.
 [http://dx.doi.org/10.1186/s13059-014-0409-z] [PMID: 25070500]

[34]
Thomas LF, Sætrom P. Circular RNAs are depleted of polymorphisms at microRNA binding sites. Bioinformatics  2014; 30(16): 2243-6.
 [http://dx.doi.org/10.1093/bioinformatics/btu257] [PMID: 24764460]

[35]
Hsiao KY, Lin YC, Gupta SK, et al. Noncoding Effects of Circular RNA CCDC66 Promote Colon Cancer Growth and Metastasis. Cancer Res  2017; 77(9): 2339-50.
 [http://dx.doi.org/10.1158/0008-5472.CAN-16-1883] [PMID: 28249903]

[36]
Boeckel JN, Jaé N, Heumüller AW, et al. Identification and Characterization of Hypoxia-Regulated Endothelial Circular RNA. Circ Res  2015; 117(10): 884-90.
 [http://dx.doi.org/10.1161/CIRCRESAHA.115.306319] [PMID: 26377962]

[37]
Panda AC, Grammatikakis I, Kim KM, et al. Identification of Senescence-Associated Circular RNAs (SAC-RNAs) reveals senescence suppressor CircPVT1. Nucleic Acids Res  2017; 45(7): 4021-35.
 [http://dx.doi.org/10.1093/nar/gkw1201] [PMID: 27928058]

[38]
Li F, Zhang L, Li W, et al. Circular RNA ITCH has inhibitory effect on ESCC by suppressing the Wnt/β-catenin pathway. Oncotarget  2015; 6(8): 6001-13.
 [http://dx.doi.org/10.18632/oncotarget.3469] [PMID: 25749389]

[39]
Ashwal-Fluss R, Meyer M, Pamudurti NR, et al. circRNA biogenesis competes with pre-mRNA splicing. Mol Cell  2014; 56(1): 55-66.
 [http://dx.doi.org/10.1016/j.molcel.2014.08.019] [PMID: 25242144]

[40]
Abdelmohsen K, Panda AC, Munk R, et al. Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1. RNA Biol  2017; 14(3): 361-9.
 [http://dx.doi.org/10.1080/15476286.2017.1279788] [PMID: 28080204]

[41]
Lebedeva S, Jens M, Theil K, et al. Transcriptome-wide analysis of regulatory interactions of the RNA-binding protein HuR. Mol Cell  2011; 43(3): 340-52.
 [http://dx.doi.org/10.1016/j.molcel.2011.06.008] [PMID: 21723171]

[42]
Guarnerio J, Bezzi M, Jeong JC, et al. Oncogenic role of fusion-circRNAs derived from cancer-associated chromosomal translocations. Cell  2016; 166(4): 1055-6.
 [http://dx.doi.org/10.1016/j.cell.2016.07.035] [PMID: 27518567]

[43]
Du WW, Yang W, Chen Y, et al. Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses. Eur Heart J  2017; 38(18): 1402-12.
 [PMID: 26873092]

[44]
Du WW, Yang W, Liu E, Yang Z, Dhaliwal P, Yang BB. Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res  2016; 44(6): 2846-58.
 [http://dx.doi.org/10.1093/nar/gkw027] [PMID: 26861625]

[45]
Chen CY, Sarnow P. Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs. Science  1995; 268(5209): 415-7.
 [http://dx.doi.org/10.1126/science.7536344] [PMID: 7536344]

[46]
Legnini I, Di Timoteo G, Rossi F, et al. Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis. Mol Cell  2017; 66(1): 22-37.e9.
 [http://dx.doi.org/10.1016/j.molcel.2017.02.017] [PMID: 28344082]

[47]
Draz MS, Fang BA, Zhang P, et al. Nanoparticle-mediated systemic delivery of siRNA for treatment of cancers and viral infections. Theranostics  2014; 4(9): 872-92.
 [http://dx.doi.org/10.7150/thno.9404] [PMID: 25057313]

[48]
Williford JM, Wu J, Ren Y, Archang MM, Leong KW, Mao HQ. Recent advances in nanoparticle-mediated siRNA delivery. Annu Rev Biomed Eng  2014; 16: 347-70.
 [http://dx.doi.org/10.1146/annurev-bioeng-071813-105119] [PMID: 24905873]

[49]
Awan FM, Yang BB, Naz A, et al. The emerging role and significance of circular RNAs in viral infections and antiviral immune responses: Possible implication as theranostic agents. RNA Biol  2021; 18(1): 1-15.
 [http://dx.doi.org/10.1080/15476286.2020.1790198] [PMID: 32615049]

[50]
Yang W, Du WW, Li X, Yee AJ, Yang BB. Foxo3 activity promoted by non-coding effects of circular RNA and Foxo3 pseudogene in the inhibition of tumor growth and angiogenesis. Oncogene  2016; 35(30): 3919-31.
 [http://dx.doi.org/10.1038/onc.2015.460] [PMID: 26657152]

[51]
Meganck RM, Borchardt EK, Castellanos Rivera RM, et al. Tissue-dependent expression and translation of circular RNAs with recombinant AAV vectors in vivo. Mol Ther Nucleic Acids  2018; 13: 89-98.
 [http://dx.doi.org/10.1016/j.omtn.2018.08.008] [PMID: 30245471]

[52]
Müller S, Appel B. In vitro circularization of RNA. RNA Biol  2017; 14(8): 1018-27.
 [http://dx.doi.org/10.1080/15476286.2016.1239009] [PMID: 27668458]

[53]
Chen YG, Chen R, Ahmad S, et al. N6-methyladenosine modification controls circular RNA immunity. Mol Cell  2019; 76(1): 96-109.
 [http://dx.doi.org/10.1016/j.molcel.2019.07.016]

[54]
Holdt LM, Kohlmaier A, Teupser D. Circular RNAs as therapeutic agents and targets. Front Physiol  2018; 9: 1262.
 [http://dx.doi.org/10.3389/fphys.2018.01262] [PMID: 30356745]

[55]
Wang AZ, Langer R, Farokhzad OC. Nanoparticle delivery of cancer drugs. Annu Rev Med  2012; 63: 185-98.
 [http://dx.doi.org/10.1146/annurev-med-040210-162544] [PMID: 21888516]

[56]
Ma X, Zhao Y, Liang XJ. Theranostic nanoparticles engineered for clinic and pharmaceutics. Acc Chem Res  2011; 44(10): 1114-22.
 [http://dx.doi.org/10.1021/ar2000056] [PMID: 21732606]

[57]
Mura S, Nicolas J, Couvreur P. Stimuli-responsive nanocarriers for drug delivery. Nat Mater  2013; 12(11): 991-1003.
 [http://dx.doi.org/10.1038/nmat3776] [PMID: 24150417]

[58]
Chen L, Watson C, Morsch M, et al. Improving the delivery of SOD1 antisense oligonucleotides to motor neurons using calcium phosphate-lipid nanoparticles. Front Neurosci  2017; 11: 476.
 [http://dx.doi.org/10.3389/fnins.2017.00476] [PMID: 28912673]

[59]
Oliveira ACN, Fernandes J, Gonçalves A, Gomes AC, Oliveira MECDR. Lipid-based nanocarriers for siRNA delivery: Challenges, strategies and the lessons learned from the DODAX: MO liposomal system. Curr Drug Targets  2019; 20(1): 29-50.
 [http://dx.doi.org/10.2174/1389450119666180703145410] [PMID: 29968536]

[60]
Kulkarni JA, Witzigmann D, Chen S, Cullis PR, van der Meel R. Lipid nanoparticle technology for clinical translation of siRNA therapeutics. Acc Chem Res  2019; 52(9): 2435-44.
 [http://dx.doi.org/10.1021/acs.accounts.9b00368] [PMID: 31397996]

[61]
Shi X, Wang B, Feng X, Xu Y, Lu K, Sun M. circRNAs and exosomes: A mysterious frontier for human cancer. Mol Ther Nucleic Acids  2020; 19: 384-92.
 [http://dx.doi.org/10.1016/j.omtn.2019.11.023] [PMID: 31887549]

[62]
Xiong S, Peng H, Ding X, et al. Circular RNA Expression Profiling and the Potential Role of hsa_circ_0089172 in Hashimoto’s Thyroiditis via Sponging miR125a-3p. Mol Ther Nucleic Acids  2019; 17: 38-48.
 [http://dx.doi.org/10.1016/j.omtn.2019.05.004] [PMID: 31207490]

[63]
Liang G, Yang Y, Niu G, Tang Z, Li K. Genome-wide profiling of Sus scrofa circular RNAs across nine organs and three developmental stages. DNA Res  2017; 24(5): 523-35.
 [http://dx.doi.org/10.1093/dnares/dsx022] [PMID: 28575165]

[64]
Jeck WR, Sharpless NE. Detecting and characterizing circular RNAs. Nat Biotechnol  2014; 32(5): 453-61.
 [http://dx.doi.org/10.1038/nbt.2890] [PMID: 24811520]

[65]
Salzman J, Chen RE, Olsen MN, Wang PL, Brown PO. Cell-type specific features of circular RNA expression. PLoS Genet  2013; 9(9): e1003777.
 [http://dx.doi.org/10.1371/journal.pgen.1003777] [PMID: 24039610]

[66]
Zhao W, Cheng Y, Zhang C, et al. Genome-wide identification and characterization of circular RNAs by high throughput sequencing in soybean. Sci Rep  2017; 7(1): 5636.
 [http://dx.doi.org/10.1038/s41598-017-05922-9] [PMID: 28717203]

[67]
Xing M. Recent advances in molecular biology of thyroid cancer and their clinical implications. Otolaryngol Clin North Am  2008; 41(6): 1135-46. ix.
 [http://dx.doi.org/10.1016/j.otc.2008.07.001] [PMID: 19040974]

[68]
Murugan AK, Xing M. Anaplastic thyroid cancers harbor novel oncogenic mutations of the ALK gene. Cancer Res  2011; 71(13): 4403-11.
 [http://dx.doi.org/10.1158/0008-5472.CAN-10-4041] [PMID: 21596819]

[69]
Hou P, Liu D, Xing M. Genome-wide alterations in gene methylation by the BRAF V600E mutation in papillary thyroid cancer cells. Endocr Relat Cancer  2011; 18(6): 687-97.
 [http://dx.doi.org/10.1530/ERC-11-0212] [PMID: 21937738]

[70]
Jo YS, Li S, Song JH, et al. Influence of the BRAF V600E mutation on expression of vascular endothelial growth factor in papillary thyroid cancer. J Clin Endocrinol Metab  2006; 91(9): 3667-70.
 [http://dx.doi.org/10.1210/jc.2005-2836] [PMID: 16772349]

[71]
Kumagai A, Namba H, Mitsutake N, et al. Childhood thyroid carcinoma with BRAFT1799A mutation shows unique pathological features of poor differentiation. Oncol Rep  2006; 16(1): 123-6.
 [http://dx.doi.org/10.3892/or.16.1.123] [PMID: 16786134]

[72]
Palona I, Namba H, Mitsutake N, et al. BRAFV600E promotes invasiveness of thyroid cancer cells through nuclear factor kappaB activation. Endocrinology  2006; 147(12): 5699-707.
 [http://dx.doi.org/10.1210/en.2006-0400] [PMID: 16959844]

[73]
Mesa C Jr, Mirza M, Mitsutake N, et al. Conditional activation of RET/PTC3 and BRAFV600E in thyroid cells is associated with gene expression profiles that predict a preferential role of BRAF in extracellular matrix remodeling. Cancer Res  2006; 66(13): 6521-9.
 [http://dx.doi.org/10.1158/0008-5472.CAN-06-0739] [PMID: 16818623]

[74]
Franzoni A, Dima M, D'Agostino M, et al. Prohibitin is overexpressed in papillary thyroid carcinomas bearing the BRAF(V600E) mutation. Thyroid  2009; 19(3): 247-55.

[75]
Watanabe R, Hayashi Y, Sassa M, et al. Possible involvement of BRAFV600E in altered gene expression in papillary thyroid cancer. Endocr J  2009; 56(3): 407-14.
 [http://dx.doi.org/10.1507/endocrj.K08E-329] [PMID: 19194051]

[76]
Zerilli M, Zito G, Martorana A, et al. BRAF(V600E) mutation influences hypoxia-inducible factor-1alpha expression levels in papillary thyroid cancer. Mod Pathol  2010; 23(8): 1052-60.

[77]
Pasquali D, Santoro A, Bufo P, et al. Upregulation of endocrine gland-derived vascular endothelial growth factor in papillary thyroid cancers displaying infiltrative patterns, lymph node metastases, and BRAF mutation. Thyroid  2011; 21(4): 391-9.
 [http://dx.doi.org/10.1089/thy.2010.0168]

[78]
Nowicki TS, Zhao H, Darzynkiewicz Z, et al. Downregulation of uPAR inhibits migration, invasion, proliferation, FAK/PI3K/Akt signaling and induces senescence in papillary thyroid carcinoma cells. Cell Cycle  2011; 10(1): 100-7.
 [http://dx.doi.org/10.4161/cc.10.1.14362] [PMID: 21191179]

[79]
Nucera C, Porrello A, Antonello ZA, et al. B-Raf(V600E) and thrombospondin-1 promote thyroid cancer progression. Proc Natl Acad Sci USA  2010; 107(23): 10649-54.
 [http://dx.doi.org/10.1073/pnas.1004934107] [PMID: 20498063]

[80]
Ringel MD, Hayre N, Saito J, et al. Overexpression and overactivation of Akt in thyroid carcinoma. Cancer Res  2001; 61(16): 6105-11.
 [PMID: 11507060]

[81]
Vasko V, Saji M, Hardy E, et al. Akt activation and localisation correlate with tumour invasion and oncogene expression in thyroid cancer. J Med Genet  2004; 41(3): 161-70.
 [http://dx.doi.org/10.1136/jmg.2003.015339] [PMID: 14985374]

[82]
Abbosh PH, Nephew KP. Multiple signaling pathways converge on beta-catenin in thyroid cancer. Thyroid  2005; 15(6): 551-61.

[83]
Pacifico F, Mauro C, Barone C, et al. Oncogenic and anti-apoptotic activity of NF-kappa B in human thyroid carcinomas. J Biol Chem  2004; 279(52): 54610-9.
 [http://dx.doi.org/10.1074/jbc.M403492200] [PMID: 15475567]

[84]
Oh HJ, Lee KK, Song SJ, et al. Role of the tumor suppressor RASSF1A in Mst1-mediated apoptosis. Cancer Res  2006; 66(5): 2562-9.
 [http://dx.doi.org/10.1158/0008-5472.CAN-05-2951] [PMID: 16510573]

[85]
Xing M, Cohen Y, Mambo E, et al. Early occurrence of RASSF1A hypermethylation and its mutual exclusion with BRAF mutation in thyroid tumorigenesis. Cancer Res  2004; 64(5): 1664-8.
 [http://dx.doi.org/10.1158/0008-5472.CAN-03-3242] [PMID: 14996725]

[86]
Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell  2012; 149(6): 1192-205.
 [http://dx.doi.org/10.1016/j.cell.2012.05.012] [PMID: 22682243]

[87]
Garcia-Rostan G, Camp RL, Herrero A, Carcangiu ML, Rimm DL, Tallini G. Beta-catenin dysregulation in thyroid neoplasms: Down-regulation, aberrant nuclear expression, and CTNNB1 exon 3 mutations are markers for aggressive tumor phenotypes and poor prognosis. Am J Pathol  2001; 158(3): 987-96.
 [http://dx.doi.org/10.1016/S0002-9440(10)64045-X] [PMID: 11238046]

[88]
Castellone MD, De Falco V, Rao DM, et al. The beta-catenin axis integrates multiple signals downstream from RET/papillary thyroid carcinoma leading to cell proliferation. Cancer Res  2009; 69(5): 1867-76.
 [http://dx.doi.org/10.1158/0008-5472.CAN-08-1982] [PMID: 19223551]

[89]
Burrows N, Resch J, Cowen RL, et al. Expression of hypoxia-inducible factor 1 alpha in thyroid carcinomas. Endocr Relat Cancer  2010; 17(1): 61-72.
 [http://dx.doi.org/10.1677/ERC-08-0251] [PMID: 19808899]

[90]
Bi W, Huang J, Nie C, et al. CircRNA circRNA_102171 promotes papillary thyroid cancer progression through modulating CTNNBIP1-dependent activation of β-catenin pathway. J Exp Clin Cancer Res  2018; 37(1): 275.
 [http://dx.doi.org/10.1186/s13046-018-0936-7] [PMID: 30424816]

[91]
Chen F, Feng Z, Zhu J, et al. Emerging roles of circRNA_NEK6 targeting miR-370-3p in the proliferation and invasion of thyroid cancer via Wnt signaling pathway. Cancer Biol Ther  2018; 19(12): 1139-52.
 [http://dx.doi.org/10.1080/15384047.2018.1480888] [PMID: 30207869]

[92]
Ye M, Hou H, Shen M, Dong S, Zhang T. Circular RNA circFOXM1 Plays a Role in Papillary Thyroid Carcinoma by Sponging miR-1179 and Regulating HMGB1 Expression. Mol Ther Nucleic Acids  2020; 19: 741-50.
 [http://dx.doi.org/10.1016/j.omtn.2019.12.014] [PMID: 31951855]

[93]
Zhang H, Ma XP, Li X, Deng FS. Circular RNA circ_0067934 exhaustion expedites cell apoptosis and represses cell proliferation, migration and invasion in thyroid cancer via sponging miR-1304 and regulating CXCR1 expression. Eur Rev Med Pharmacol Sci  2019; 23(24): 10851-66.
 [PMID: 31858554]

[94]
Yao Y, Chen X, Yang H, et al. Hsa_circ_0058124 promotes papillary thyroid cancer tumorigenesis and invasivenessthrough the NOTCH3/GATAD2A axis. 2019; 38(1): 318.

[95]
Yang Y, Ding L, Li Y, Xuan C. Hsa_circ_0039411 promotes tumorigenesis and progression of papillary thyroid cancer by miR-1179/ABCA9 and miR-1205/MTA1 signaling pathways. 2020; 235(2): 1321-9.

[96]
Liu W, Zhao J, Jin M, Zhou M. circRAPGEF5 contributes to papillary thyroid proliferation and metastatis by regulation miR-198/FGFR1. Mol Ther Nucleic Acids  2019; 14: 609-16.
 [http://dx.doi.org/10.1016/j.omtn.2019.01.003] [PMID: 30785065]

[97]
Wang H, Yan X, Zhang H, Zhan X. CircRNA circ_0067934 overexpression correlates with poor prognosis and promotes thyroid carcinoma progression. Med Sci Monit  2019; 25: 1342-9.
 [http://dx.doi.org/10.12659/MSM.913463] [PMID: 30779728]

[98]
Pan Y, Xu T, Liu Y, Li W, Zhang W. Upregulated circular RNA circ_0025033 promotes papillary thyroid cancer cell proliferation and invasion via sponging miR-1231 and miR-1304. Biochem Biophys Res Commun  2019; 510(2): 334-8.
 [http://dx.doi.org/10.1016/j.bbrc.2019.01.108] [PMID: 30709584]

[99]
Liu F, Zhang J, Qin L, et al. 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)  2018; 10(12): 3806-20.
 [http://dx.doi.org/10.18632/aging.101674] [PMID: 30540564]

[100]
Li X, Tian Y, Hu Y, Yang Z, Zhang L, Luo J. CircNUP214 sponges miR-145 to promote the expression of ZEB2 in thyroid cancer cells. Biochem Biophys Res Commun  2018; 507(1-4): 168-72.
 [http://dx.doi.org/10.1016/j.bbrc.2018.10.200] [PMID: 30415780]

[101]
Jin X, Wang Z, Pang W, et al. Upregulated hsa_circ_0004458 contributes to progression of papillary thyroid carcinoma by inhibition of miR-885-5p and activation of RAC1. Med Sci Monit  2018; 24: 5488-500.
 [http://dx.doi.org/10.12659/MSM.911095] [PMID: 30086127]

[102]
Wei H, Pan L, Tao D, Li R. Circular RNA circZFR contributes to papillary thyroid cancer cell proliferation and invasion by sponging miR-1261 and facilitating C8orf4 expression. Biochem Biophys Res Commun  2018; 503(1): 56-61.
 [http://dx.doi.org/10.1016/j.bbrc.2018.05.174] [PMID: 29842886]

[103]
Wang M, Chen B, Ru Z, Cong L. CircRNA circ-ITCH suppresses papillary thyroid cancer progression through miR-22-3p/CBL/β-catenin pathway. Biochem Biophys Res Commun  2018; 504(1): 283-8.
 [http://dx.doi.org/10.1016/j.bbrc.2018.08.175] [PMID: 30190130]

[104]
Lan X, Cao J, Xu J, et al. Decreased expression of hsa_circ_0137287 predicts aggressive clinicopathologic characteristics in papillary thyroid carcinoma. J Clin Lab Anal  2018; 32(8): e22573.
 [http://dx.doi.org/10.1002/jcla.22573] [PMID: 29790216]
Cite As
Current Molecular Medicine

CircRNAs: A Novel Strategy in Diagnosis and Treatment of Thyroid Cancer

Abstract
