Skip to main content
SpringerLink
Log in

MicroRNA deregulation in parathyroid tumours suggests an embryonic signature

  • Short Review
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Primary hyperparathyroidism is a common endocrine disorder caused by abnormal tumour parathyroid cell proliferation. Parathyroid tumours show a great variability both in clinical features, such as the severity of PTH secretion, the rate and the pattern of cell proliferation, and genetic background. Studies aiming to develop new diagnostic markers and therapeutic approaches need a deeper definition of this variability. Dysregulation of microRNAs (miRNAs) has been shown to play an essential role in the development and progression of cancer. MiRNAs are small noncoding RNAs that inhibit the translation and stability of messenger RNAs (mRNAs). Here, data about the miRNA expression pattern in parathyroid normal and tumour glands were reviewed. Though available data in parathyroid tumours are very limited, the expression pattern of a subset of specific miRNAs clearly discriminated parathyroid carcinomas from normal parathyroid glands and, more clinically relevant, from parathyroid adenomas. Investigation showed that parathyroid tumours were characterized by an embryonic expression pattern of miRNAs such as miR-296, or the miRNA clusters C19MC and miR-371-3, typically in stem cells committed to differentiation or during human embryonic development, respectively. Further, miRNA profiles were correlated with tumour aggressive behaviour. Moreover, the interaction with the oncosuppressor menin suggests that miRNAs might modulate the function of the known oncosuppressors or oncogenes involved in parathyroid tumourigenesis and thus overseeing the tumour phenotype. In conclusion, miRNAs might provide new diagnostic markers and new therapeutic approaches by developing molecular miRNA-targeted therapies for the cure of parathyroid tumours, whose unique option is surgery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Alvelos MI, Vinagre J, Fonseca E, Barbosa E, Teixera-Gomes J, Sobrinho-Simões M, Soares P (2012) MEN1 intragenic deletions may represent the most prevalent somatic event in sporadic primary hyperparathyroidism. Eur J Endocrinol 168:119–128

    Article  PubMed  Google Scholar 

  2. Newey PJ, Nesbit MA, Rimmer AJ, Attar M, Head RT, Christie PT, Gorvin CM, Stechman M, Gregory L, Mihai R, Sadler G, McVean G, Buck D, Thakker RV (2012) Whole-exome sequencing studies of nonhereditary (sporadic) parathyroid adenomas. J Clin Endocrinol Metab 97:E1995–E2005

    Article  CAS  PubMed  Google Scholar 

  3. Lee M, Pellegatta NS (2013) Multiple endocrine neoplasia syndrome associated with mutation of p27. J Endocrinol Invest 36:781–787

    CAS  PubMed  Google Scholar 

  4. Cetani F, Pardi E, Borsari S, Viacava P, Dipollina G, Cianferotti L, Ambrogini E, Gazzerro E, Colussi G, Berti P, Miccoli P, Pinchera A, Marcocci C (2004) Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic tumors. J Clin Endocrinol Metab 89:5583–5591

    Article  CAS  PubMed  Google Scholar 

  5. Guarnieri V, Battista C, Muscarella LA, Bisceglia M, de Martino D, Baorda F, Maiello E, D’Agruma L, Chiodini I, Clemente C, Minisola S, Romagnoli E, Corbetta S, Viti R, Eller-Vainicher C, Spada A, Iacobellis M, Malavolta N, Carella M, Canaff L, Hendy GN, Cole DE, Scillitani A (2012) CDC73 mutations and parafibromin immunohistochemistry in parathyroid tumors: clinical correlations in a single-centre patient cohort. Cell Oncol (Dodr) 35:411–422

    Article  CAS  Google Scholar 

  6. Di Leva G, Garofalo M, Croce CM (2014) MicroRNAs in cancer. Annu Rev Pathol Mech Dis 9:287–314

    Article  Google Scholar 

  7. Gadelha MR, Kasuki L, Dénes J, Trivellin G, Korbonits M (2013) MicroRNAs: suggested role in pituitary adenoma pathogenesis. J Endocrinol Invest 36:889–895

    Article  CAS  PubMed  Google Scholar 

  8. Zsippai A, Szabó PM, Szabó DR, Bagy Z, Patócs A, Rácz K, Igaz P (2013) In silico analysis of pathways affected by differentially expressed microRNA in adrenocortical tumors. J Endocrinol Invest 36:1011–1019

    CAS  PubMed  Google Scholar 

  9. Corbetta S, Vaira V, Guarnieri V, Scillitani A, Eller-Vainicher C, Ferrero S, Vicentini L, Chiodini I, Bisceglia M, Beck-Peccoz P, Bosari S, Spada A (2010) Differential expression of microRNAs in human parathyroid carcinomas compared with normal parathyroid tissue. Endocr Relat Cancer 17:135–146

    Article  CAS  PubMed  Google Scholar 

  10. Rahbari R, Holloway AK, He M, Khanafshar E, Clark OH, Kebebew E (2011) Identification of differentially expressed microRNA in parathyroid tumors. Ann Surg Oncol 18:1158–1165

    Article  PubMed Central  PubMed  Google Scholar 

  11. Vaira V, Faversani A, Dohi T, Montorsi M, Augello C, Gatti S, Coggi G, Altieri DC, Bosari S (2012) miR-296 regulation of a cell polarity-cell plasticity module controls tumor progression. Oncogene 31:27–38

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Vaira V, Elli F, Forno I, Guarnieri V, Verdelli C, Ferrero S, Scillitani A, Vicentini L, Cetani F, Mantovani G, Spada A, Bosari S, Corbetta S (2012) The microRNA cluster C19MC is deregulated in parathyroid tumours. J Mol Endocrinol 49:115–124

    Article  CAS  PubMed  Google Scholar 

  13. Luzi E, Marini F, Giusti F, Galli G, Cavalli L, Brandi ML (2012) The negative feedback-loop between the oncomir Mir-24-1 and menin modulates the Men1 tumorigenesis by mimicking the “Knudson’s second hit”. PLoS One 7:e39767

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Imanishi Y, Tahara H (2001) Putative parathyroid tumor suppressor on 1 p: independent molecular mechanisms of tumorigenesis from 11q allelic loss. Am J Kidney Dis 38:S165–S167

    Article  CAS  PubMed  Google Scholar 

  15. Cryns VL, Yi SM, Tahara H, Gaz RD, Arnold A (1995) Frequent loss of chromosome arm 1p DNA in parathyroid adenomas. Genes Chromosomes Cancer 13:9–17

    Article  CAS  PubMed  Google Scholar 

  16. Palanisamy N, Imanishi Y, Rao PH, Tahara H, Chaganti RS, Arnold A (1998) Novel chromosomal abnormalities identified by comparative genomic hybridization in parathyroid adenomas. J Clin Endocrinol Metab 83:1766–1770

    CAS  PubMed  Google Scholar 

  17. Garcia JL, Tardio JC, Gutierrez NC, Gonzalez MB, Polo JR, Hernandez JM, Menarguez J (2002) Chromosomal imbalances identified by comparative genomic hybridization in sporadic parathyroid adenomas. Eur J Endocrinol 146:209–213

    Article  CAS  PubMed  Google Scholar 

  18. Sulaiman L, Nilsson IL, Juhlin CC, Haglund F, Höög A, Larsson C, Hashemi J (2012) Genetic characterization of large parathyroid adenomas. Endocr Relat Cancer 19:389–407

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Robson JE, Eaton SA, Underhill P, Williams D, Peters J (2012) MicroRNAs 296 and 298 are imprinted and part of the GNAS/Gnas cluster and miR-296 targets IKBKE and Tmed9. RNA 18:135–144

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Shin JY, Gupta MK, Jung YH, Uhm SJ, Lee HT (2011) Differential genomic imprinting and expression of imprinted microRNAs in testes-derived male germ-line stem cells in mouse. PLoS One 6:e22481

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Tay Y, Zhang J, Thomson AM, Lim B, Rigoutsos I (2008) MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455:1124–1128

    Article  CAS  PubMed  Google Scholar 

  22. Laurent LC, Chen J, Ulitsky I, Mueller FJ, Lu C, Shamir R, Fan JB, Loring JF (2008) Comprehensive microRNA profiling reveals a unique human embryonic stem cell signature dominated by a single seed sequence. Stem Cells 26:1506–1516

    Article  CAS  PubMed  Google Scholar 

  23. Li SS, Yu SL, Kao LP, Tsai ZY, Singh S, Chen BZ, Ho BC, Liu YH, Yang PC (2009) Target identification of microRNAs expressed highly in human embryonic stem cells. J Cell Biochem 106:1020–1030

    Article  CAS  PubMed  Google Scholar 

  24. Ren J, Jin P, Wang E, Marincola FM, Stroncek DF (2009) MicroRNA and gene expression patterns in the differentiation of human embryonic stem cells. J Transl Med 7:20

    Article  PubMed Central  PubMed  Google Scholar 

  25. Toffanin S, Alsinet C, Cornella H, Sia D, Llovet JM (2011) MicroRNAs and the MYC network: a major piece in the puzzle of liver cancer. Gastroenterology 140:2138–2140

    Article  PubMed  Google Scholar 

  26. Li M, Lee KF, Lu Y, Shih D, Clarke I, Eberhart C, Collins VP, Van Meter T, Picard D, Zhou L, Boutros PC, Modena P, Liang ML, Scherer SW, Bouffet E, Rutka JT, Pomeroy SL, Lau CC, Taylor MD, Gajjar A, Dirks PB, Hawkins CE, Huang A (2009) Frequent amplification of a chr19q13.41 microRNA polycistron in aggressive primitive neuroectodermal brain tumors. Cancer Cell 16:533–546

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Visone R, Russo L, Pallante P, De Martino I, Ferraro A, Leone V, Borbone E, Petrocca F, Alder H, Croce CM, Fusco A (2007) MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cylce. Endocr Relat Cancer 14:791–798

    Article  CAS  PubMed  Google Scholar 

  28. Galardi S, Mercatelli N, Giorda E, Massalini S, Frajese GV, Ciafrè SA, Farace MG (2007) miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1. J Biol Chem 282:23716–23724

    Article  CAS  PubMed  Google Scholar 

  29. Ebrahimi F, Gopalan V, Smith RA, Lam AK (2014) MiR-126 in human cancers: clinical roles and current perspectives. Exp Mol Pathol 96:98–107

    Article  CAS  PubMed  Google Scholar 

  30. Rogler CE, Levoci L, Ader T, Massimi A, Tchaikovskaya T, Norel R, Rogler LE (2009) MicroRNA-23b cluster microRNAs regulate transforming growth factor-beta/bone morphogenetic protein signaling and liver stem cell differentiation by targeting Smads. Hepatology 50:575–584

    Article  CAS  PubMed  Google Scholar 

  31. Rather MI, Nagashri MN, Swamy SS, Gopinath KS, Kumar A (2013) Oncogenic microRNA-155 down-regulates tumor suppressor CDC73 and promotes oral cell squamous cell carcinoma cell proliferation: implications for cancer therapeutics. J Biol Chem 288:608–618

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Gong Y, Renigunta V, Himmerkus N, Zhang J, Renigunta A, Bleich M, Hou J (2012) Claudin-14 regulates renal Ca++ transport in response to CASR signaling via a novel microRNA pathway. EMBO J 31:1999–2012

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Gurung B, Bari AM, Hua X (2014) Menin is required for optimal processing of the microRNA let-7a. J Biol Chem 289:9902–9908

    Article  CAS  PubMed  Google Scholar 

  34. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

All the authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Author information

Authors and Affiliations

  1. Laboratory of Molecular Biology, IRCCS Policlinico San Donato, San Donato Milanese, MI, Italy

    C. Verdelli

  2. Division of Pathology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    I. Forno & V. Vaira

  3. Endocrinology and Diabetology Unit, Department of Biomedical Sciences, University of Milan, IRCCS Policlinico San Donato, Via Morandi 30, 20097, San Donato Milanese, MI, Italy

    S. Corbetta

Authors
  1. C. Verdelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Forno
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. Vaira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Corbetta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Corbetta.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Verdelli, C., Forno, I., Vaira, V. et al. MicroRNA deregulation in parathyroid tumours suggests an embryonic signature. J Endocrinol Invest 38, 383–388 (2015). https://doi.org/10.1007/s40618-014-0234-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-014-0234-y

Keywords

Search

Navigation