lncRNA DIRC3 regulates invasiveness and insulin-like growth factor signaling in thyroid cancer cells

in Endocrine-Related Cancer
Authors:
Piotr T Wysocki Laboratory of Experimental Medicine, Medical University of Warsaw, Warsaw, Poland
Department of Oncology, Medical University of Warsaw, Warsaw, Poland

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https://orcid.org/0000-0002-9436-5419
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Karol Czubak Laboratory of Experimental Medicine, Medical University of Warsaw, Warsaw, Poland

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Anna A Marusiak Laboratory of Molecular OncoSignalling, IMol Polish Academy of Sciences, Warsaw, Poland

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Monika Kolanowska Warsaw Genomics INC, Warsaw, Poland

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Dominika Nowis Laboratory of Experimental Medicine, Medical University of Warsaw, Warsaw, Poland
Department of Immunology, Medical University of Warsaw, Warsaw, Poland

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Correspondence should be addressed to P T Wysocki: piotr.wysocki@wum.edu.pl
DOI:
https://doi.org/10.1530/ERC-23-0058
Volume/Issue:
Volume 30: Issue 8
Article Type:
Research Article
Article ID:
e230058
Online Publication Date:
26 Jun 2023
Copyright:
© the author(s) 2023
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Differentiated thyroid cancers (DTCs) are malignancies that demonstrate strong but largely uncharacterized heritability. Germline variants that influence the risk of DTCs localize in disrupted in renal carcinoma 3 (DIRC3), a poorly described long non-coding RNA gene. Here, we investigated the function of DIRC3 in DTCs. Using patient-matched thyroid tissue pairs and The Cancer Genome Atlas data, we established that DIRC3 is downregulated in DTCs, whereas high expression of DIRC3 in tumors may reduce the risk of cancer recurrence. DIRC3 transcripts were enriched in cell nuclei, where they upregulated insulin-like growth factor binding protein 5 (IGFBP5), a gene that modulates the cellular response to insulin-like growth factor 1 (IGF1). Silencing DIRC3 in thyroid cancer cell lines (MDA-T32 and MDA-T120) had a dichotomous phenotypic influence: augmented cell migration and invasiveness, reduced apoptosis, but abrogated the MTT reduction rate. Transcriptomic profiling and gene rescue experiments indicated the functional redundancy in the activities of DIRC3 and IGFBP5. Moreover, the reduced level of DIRC3 enhanced the susceptibility of thyroid cancer cells to IGF1 stimulation and promoted Akt signaling via downregulation of the IGFBP5 protein. In conclusion, DIRC3 expression alters the phenotype of thyroid cancer cells and regulates the activity of the IGFBP5/IGF1/Akt axis. Our findings suggest that an interplay between DIRC3 and IGF signaling may play a role in promoting thyroid carcinogenesis.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2023
Article ID:
e230058
Received Date:
26 Apr 2023
Accepted Date:
02 May 2023
Print Publication Date:
01 Aug 2023
Online Publication Date:
26 Jun 2023
Keywords:
DIRC3; thyroid cancer; IGFBP5; IGF1; invasiveness

  • Amundadottir LT, Thorvaldsson S, Gudbjartsson DF, Sulem P, Kristjansson K, Arnason S, Gulcher JR, Bjornsson J, Kong A, Thorsteinsdottir U, et al.2004 Cancer as a complex phenotype: pattern of cancer distribution within and beyond the nuclear family. PLOS Medicine 1 e65. (https://doi.org/10.1371/journal.pmed.0010065)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Argente J, Chowen JA, Perez-Jurado LA, Frystyk J & & Oxvig C 2017 One level up: abnormal proteolytic regulation of IGF activity plays a role in human pathophysiology. EMBO Molecular Medicine 9 1338–1345. (https://doi.org/10.15252/emmm.201707950)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Baloch ZW, Asa SL, Barletta JA, Ghossein RA, Juhlin CC, Jung CK, LiVolsi VA, Papotti MG, Sobrinho-Simões M, Tallini G, et al.2022 Overview of the 2022 WHO classification of thyroid neoplasms. Endocrine Pathology 33 27–63. (https://doi.org/10.1007/s12022-022-09707-3)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Becker MA, Hou X, Harrington SC, Weroha SJ, Gonzalez SE, Jacob KA, Carboni JM, Gottardis MM & & Haluska P 2012 IGFBP ratio confers resistance to IGF targeting and correlates with increased invasion and poor outcome in breast tumors. Clinical Cancer Research 18 1808–1817. (https://doi.org/10.1158/1078-0432.CCR-11-1806)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bodmer D, Schepens M, Eleveld MJ, Schoenmakers EF & & Geurts van Kessel A 2003 Disruption of a novel gene, DIRC3, and expression of DIRC3-HSPBAP1 fusion transcripts in a case of familial renal cell cancer and t(2;3)(q35;q21). Genes, Chromosomes and Cancer 38 107–116. (https://doi.org/10.1002/gcc.10243)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bumber B, Marjanovic Kavanagh M, Jakovcevic A, Sincic N, Prstacic R & & Prgomet D 2020 Role of matrix metalloproteinases and their inhibitors in the development of cervical metastases in papillary thyroid cancer. Clinical Otolaryngology 45 55–62. (https://doi.org/10.1111/coa.13466)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cabanillas ME, McFadden DG & & Durante C 2016 Thyroid cancer. Lancet 388 2783–2795. (https://doi.org/10.1016/S0140-6736(1630172-6)

  • Cancer Genome Atlas Research Network 2014 Integrated genomic characterization of papillary thyroid carcinoma. Cell 159 676–690. (https://doi.org/10.1016/j.cell.2014.09.050)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Coe EA 2020 Identification and characterisation of MITF-regulated long noncoding RNA candidate regulators of melanoma. Doctoral Dissertation University of Bath. (available at: https://researchportal.bath.ac.uk/en/studentTheses/identification-and-characterisation-of-mitf-regulated-long-non-co)

    • PubMed
    • Export Citation

  • Coe EA, Tan JY, Shapiro M, Louphrasitthiphol P, Bassett AR, Marques AC, Goding CR & & Vance KW 2019 The MITF-SOX10 regulated long non-coding RNA DIRC3 is a melanoma tumour suppressor. PLOS Genetics 15 e1008501. (https://doi.org/10.1371/journal.pgen.1008501)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Czene K, Lichtenstein P & & Hemminki K 2002 Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish family-cancer database. International Journal of Cancer 99 260–266. (https://doi.org/10.1002/ijc.10332)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ding M, Bruick RK & & Yu Y 2016 Secreted IGFBP5 mediates mTORC1-dependent feedback inhibition of IGF-1 signalling. Nature Cell Biology 18 319–327. (https://doi.org/10.1038/ncb3311)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Dolgin E 2020 IGF-1R drugs travel from cancer cradle to Graves’. Nature Biotechnology 38 385–388. (https://doi.org/10.1038/s41587-020-0481-8)

  • Duan C & & Allard JB 2020 Insulin-like growth factor binding Protein-5 in physiology and disease. Frontiers in Endocrinology (Lausanne) 11 100–100. (https://doi.org/10.3389/fendo.2020.00100)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Duan C & & Clemmons DR 1998 Differential expression and biological effects of insulin-like growth factor-binding protein-4 and -5 in vascular smooth muscle cells. Journal of Biological Chemistry 273 16836–16842. (https://doi.org/10.1074/jbc.273.27.16836)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Duan C, Hawes SB, Prevette T & & Clemmons DR 1996 Insulin-like growth factor-I (IGF-I) regulates IGF-binding protein-5 synthesis through transcriptional activation of the gene in aortic smooth muscle cells. Journal of Biological Chemistry 271 4280–4288. (https://doi.org/10.1074/jbc.271.8.4280)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Duan C, Liimatta MB & & Bottum OL 1999 Insulin-like growth factor (IGF)-I regulates IGF-binding protein-5 gene expression through the phosphatidylinositol 3-kinase, protein kinase B/Akt, and p70 S6 kinase signaling pathway. Journal of Biological Chemistry 274 37147–37153. (https://doi.org/10.1074/jbc.274.52.37147)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Fachal L, Aschard H, Beesley J, Barnes DR, Allen J, Kar S, Pooley KA, Dennis J, Michailidou K, Turman C, et al.2020 Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes. Nature Genetics 52 56–73. (https://doi.org/10.1038/s41588-019-0537-1)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Fukuda R, Hirota K, Fan F, Jung YD, Ellis LM & & Semenza GL 2002 Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. Journal of Biological Chemistry 277 38205–38211. (https://doi.org/10.1074/jbc.M203781200)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ghoussaini M, Edwards SL, Michailidou K, Nord S, Cowper-Sal Lari R, Desai K, Kar S, Hillman KM, Kaufmann S, Glubb DM, et al.2014 Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation. Nature Communications 4 4999. (https://doi.org/10.1038/ncomms5999)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gou Q, Gao L, Nie X, Pu W, Zhu J, Wang Y, Liu X, Tan S, Zhou JK, Gong Y, et al.2018 Long noncoding RNA AB074169 inhibits cell proliferation via modulation of KHSRP-mediated CDKN1a expression in papillary thyroid carcinoma. Cancer Research 78 4163–4174. (https://doi.org/10.1158/0008-5472.CAN-17-3766)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • GTEx Consortium, Thomas J, , Salvatore M, , Phillips R, , Lo E, , Shad S, , Hasz R, , Walters G, , Garcia F, & Young N2013 The Genotype-Tissue Expression (GTEx) project. Nature Genetics 45 580–585. (https://doi.org/10.1038/ng.2653)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gudmundsson J, Sulem P, Gudbjartsson DF, Jonasson JG, Masson G, He H, Jonasdottir A, Sigurdsson A, Stacey SN, Johannsdottir H, et al.2012 Discovery of common variants associated with low TSH levels and thyroid cancer risk. Nature Genetics 44 319–322. (https://doi.org/10.1038/ng.1046)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gudmundsson J, Thorleifsson G, Sigurdsson JK, Stefansdottir L, Jonasson JG, Gudjonsson SA, Gudbjartsson DF, Masson G, Johannsdottir H, Halldorsson GH, et al.2017 A genome-wide association study yields five novel thyroid cancer risk loci. Nature Communications 8 14517. (https://doi.org/10.1038/ncomms14517)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Guibon J, Sugier PE, Kulkarni O, Karimi M, Bacq-Daian D, Besse C, Boland A, Adjadj E, Rachédi F, Rubino C, et al.2021 Fine-mapping of two differentiated thyroid carcinoma susceptibility loci at 2q35 and 8p12 in Europeans, Melanesians and Polynesians. Oncotarget 12 493–506. (https://doi.org/10.18632/oncotarget.27888)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Humphrey J, Birsa N, Milioto C, McLaughlin M, Ule AM, Robaldo D, Eberle AB, Kräuchi R, Bentham M, Brown AL, et al.2020 FUS ALS-causative mutations impair FUS autoregulation and splicing factor networks through intron retention. Nucleic Acids Research 48 6889–6905. (https://doi.org/10.1093/nar/gkaa410)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Iams WT & & Lovly CM 2015 Molecular pathways: clinical applications and future direction of insulin-like growth factor-1 receptor pathway blockade. Clinical Cancer Research 21 4270–4277. (https://doi.org/10.1158/1078-0432.CCR-14-2518)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Jing Z, Hou X, Liu Y, Yan S, Wang R, Zhao S & & Wang Y 2015 Association between height and thyroid cancer risk: a meta-analysis of prospective cohort studies. International Journal of Cancer 137 1484–1490. (https://doi.org/10.1002/ijc.29487)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kitahara CM, Gamborg M, Berrington de González A, Sørensen TIA & & Baker JL 2014 Childhood height and body mass index were associated with risk of adult thyroid cancer in a large cohort study. Cancer Research 74 235–242. (https://doi.org/10.1158/0008-5472.CAN-13-2228)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Knuppel A, Fensom GK, Watts EL, Gunter MJ, Murphy N, Papier K, Perez-Cornago A, Schmidt JA, Smith Byrne K, Travis RC, et al.2020 Circulating insulin-like growth factor-I concentrations and risk of 30 cancers: prospective analyses in UK Biobank. Cancer Research 80 4014–4021. (https://doi.org/10.1158/0008-5472.CAN-20-1281)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Köhler A, Chen B, Gemignani F, Elisei R, Romei C, Figlioli G, Cipollini M, Cristaudo A, Bambi F, Hoffmann P, et al.2013 Genome-wide association study on differentiated thyroid cancer. Journal of Clinical Endocrinology and Metabolism 98 E1674–E1681. (https://doi.org/10.1210/jc.2013-1941)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lango Allen H, Estrada K, Lettre G, Berndt SI, Weedon MN, Rivadeneira F, Willer CJ, Jackson AU, Vedantam S, Raychaudhuri S, et al.2010 Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467 832–838. (https://doi.org/10.1038/nature09410)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liu H, Li R, Guan L & & Jiang T 2018 Knockdown of lncRNA UCA1 inhibits proliferation and invasion of papillary thyroid carcinoma through regulating miR-204/IGFBP5 axis. OncoTargets and Therapy 11 7197–7204. (https://doi.org/10.2147/OTT.S175467)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liu L, Wang J, Li X, Ma J, Shi C, Zhu H, Xi Q, Zhang J, Zhao X & & Gu M 2015 MiR-204-5p suppresses cell proliferation by inhibiting IGFBP5 in papillary thyroid carcinoma. Biochemical and Biophysical Research Communications 457 621–626. (https://doi.org/10.1016/j.bbrc.2015.01.037)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liyanarachchi S, Wojcicka A, Li W, Czetwertynska M, Stachlewska E, Nagy R, Hoag K, Wen B, Ploski R, Ringel MD, et al.2013 Cumulative risk impact of five genetic variants associated with papillary thyroid carcinoma. Thyroid 23 1532–1540. (https://doi.org/10.1089/thy.2013.0102)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lonsdale J, Thomas J, Salvatore M, Phillips R, Lo E, Shad S, Hasz R, Walters G, Garcia F, Young N et al.. 2013 The Genotype-Tissue Expression (GTEx) project. Nature Genetics 45 580–585. (https://doi.org/10.1038/ng.2653)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Manzella L, Massimino M, Stella S, Tirrò E, Pennisi MS, Martorana F, Motta G, Vitale SR, Puma A, Romano C, et al.2019 Activation of the IGF axis in thyroid cancer: implications for tumorigenesis and treatment. International Journal of Molecular Sciences 20 3258. (https://doi.org/10.3390/ijms20133258)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Michailidou K, Hall P, Gonzalez-Neira A, Ghoussaini M, Dennis J, Milne RL, Schmidt MK, Chang-Claude J, Bojesen SE, Bolla MK, et al.2013 Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nature Genetics 45 353–361, 361.e1–361.e2. (https://doi.org/10.1038/ng.2563)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Neuzillet Y, Chapeaublanc E, Krucker C, De Koning L, Lebret T, Radvanyi F & & Bernard-Pierrot I 2017 IGF1R activation and the in vitro antiproliferative efficacy of IGF1R inhibitor are inversely correlated with IGFBP5 expression in bladder cancer. BMC Cancer 17 636. (https://doi.org/10.1186/s12885-017-3618-5)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Oakley GM, Curtin K, Pimentel R, Buchmann L & & Hunt J 2013 Establishing a familial basis for papillary thyroid carcinoma using the Utah Population Database. JAMA Otolaryngology– Head and Neck Surgery 139 1171–1174. (https://doi.org/10.1001/jamaoto.2013.4987)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ogłuszka M, Orzechowska M, Jędroszka D, Witas P & & Bednarek AK 2019 Evaluate cutpoints: adaptable continuous data distribution system for determining survival in Kaplan-Meier estimator. Computer Methods and Programs in Biomedicine 177 133–139. (https://doi.org/10.1016/j.cmpb.2019.05.023)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pavlicek A, Lira ME, Lee NV, Ching KA, Ye J, Cao J, Garza SJ, Hook KE, Ozeck M, Shi ST, et al.2013 Molecular predictors of sensitivity to the insulin-like growth factor 1 receptor inhibitor figitumumab (CP-751,871). Molecular Cancer Therapeutics 12 2929–2939. (https://doi.org/10.1158/1535-7163.MCT-13-0442-T)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rashkin SR, Graff RE, Kachuri L, Thai KK, Alexeeff SE, Blatchins MA, Cavazos TB, Corley DA, Emami NC, Hoffman JD, et al.2020 Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts. Nature Communications 11 4423. (https://doi.org/10.1038/s41467-020-18246-6)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Saenko VA & & Rogounovitch TI 2018 Genetic polymorphism predisposing to differentiated thyroid cancer: a review of major findings of the genome-wide association studies. Endocrinology and Metabolism 33 164–174. (https://doi.org/10.3803/EnM.2018.33.2.164)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sakaue S, Kanai M, Tanigawa Y, Karjalainen J, Kurki M, Koshiba S, Narita A, Konuma T, Yamamoto K, Akiyama M, et al.2021 A cross-population atlas of genetic associations for 220 human phenotypes. Nature Genetics 53 1415–1424. (https://doi.org/10.1038/s41588-021-00931-x)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Son HY, Hwangbo Y, Yoo SK, Im SW, Yang SD, Kwak SJ, Park MS, Kwak SH, Cho SW, Ryu JS, et al.2017 Genome-wide association and expression quantitative trait loci studies identify multiple susceptibility loci for thyroid cancer. Nature Communications 8 15966. (https://doi.org/10.1038/ncomms15966)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Subhash S & & Kanduri C 2016 GeneSCF: a real-time based functional enrichment tool with support for multiple organisms. BMC Bioinformatics 17 365. (https://doi.org/10.1186/s12859-016-1250-z)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Świerniak M, Wójcicka A, Czetwertyńska M, Długosińska J, Stachlewska E, Gierlikowski W, Kot A, Górnicka B, Koperski Ł, Bogdańska M, et al.2016 Association between GWAS-derived rs966423 genetic variant and overall mortality in patients with differentiated thyroid cancer. Clinical Cancer Research 22 1111–1119. (https://doi.org/10.1158/1078-0432.CCR-15-1746)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Takahashi M, Saenko VA, Rogounovitch TI, Kawaguchi T, Drozd VM, Takigawa-Imamura H, Akulevich NM, Ratanajaraya C, Mitsutake N, Takamura N, et al.2010 The FOXE1 locus is a major genetic determinant for radiation-related thyroid carcinoma in Chernobyl. Human Molecular Genetics 19 2516–2523. (https://doi.org/10.1093/hmg/ddq123)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Truong T, Lesueur F, Sugier PE, Guibon J, Xhaard C, Karimi M, Kulkarni O, Lucotte EA, Bacq-Daian D, Boland-Auge A, et al.2021 Multiethnic genome-wide association study of differentiated thyroid cancer in the EPITHYR consortium. International Journal of Cancer 148 2935–2946. (https://doi.org/10.1002/ijc.33488)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wang J, Ding N, Li Y, Cheng H, Wang D, Yang Q, Deng Y, Yang Y, Li Y, Ruan X, et al.2015 Insulin-like growth factor binding protein 5 (IGFBP5) functions as a tumor suppressor in human melanoma cells. Oncotarget 6 20636–20649. (https://doi.org/10.18632/oncotarget.4114)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wood AR, Esko T, Yang J, Vedantam S, Pers TH, Gustafsson S, Chu AY, Estrada K, Luan J, Kutalik Z, et al.2014 Defining the role of common variation in the genomic and biological architecture of adult human height. Nature Genetics 46 1173–1186. (https://doi.org/10.1038/ng.3097)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wyszynski A, Hong CC, Lam K, Michailidou K, Lytle C, Yao S, Zhang Y, Bolla MK, Wang Q, Dennis J, et al.2016 An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression. Human Molecular Genetics 25 3863–3876. (https://doi.org/10.1093/hmg/ddw223)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ye M, Dong S, Hou H, Zhang T & & Shen M 2021 Oncogenic role of long noncoding RNA MALAT1 in thyroid cancer progression through regulation of the miR-204/IGF2BP2/m6A-MYC signaling. Molecular Therapy. Nucleic Acids 23 1–12. (https://doi.org/10.1016/j.omtn.2020.09.023)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zaballos MA & & Santisteban P 2013 FOXO1 controls thyroid cell proliferation in response to TSH and IGF-I and is involved in thyroid tumorigenesis. Molecular Endocrinology 27 50–62. (https://doi.org/10.1210/me.2012-1032)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zaballos MA & & Santisteban P 2017 Key signaling pathways in thyroid cancer. Journal of Endocrinology 235 R43–R61. (https://doi.org/10.1530/JOE-17-0266)