Skip to main content

Advertisement

SpringerLink
Log in

Verification of candidate microRNA markers for parathyroid carcinoma

  • Endocrine Genetics/Epigenetics
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

Parathyroid carcinoma (PCa) is a rare endocrine malignancy with poor prognosis and is often difficult to accurately diagnose both before and after surgery. Dysregulated microRNA (miRNA) levels have been identified in PCa using a limited number of samples. The aim of the present study was to verify a group of miRNA markers in a new series of samples to explore their potential significance in PCa diagnosis.

Methods

A total of 58 tissue samples, including 17 PCa lesions and 41 sporadic parathyroid adenomas (PAds), were obtained from 56 primary hyperparathyroidism (pHPT) patients. Candidate miRNAs (miR-139-5p, miR-155-5p, miR-222-3p, miR-26b-5p, miR-296-5p, miR-30b-5p, miR-372-3p, miR-503-5p, miR-517c-3p, miR-7-5p, and miR-126-5p) were quantified by TaqMan real-time quantitative PCR assays.

Results

Up-regulated miR-222 (p = 0.041) levels and down-regulated miR-139 (p = 0.003), miR-30b (p < 0.001), miR-517c (p = 0.038), and miR-126* (p = 0.002) levels were found in PCa relative to PAd. Binary logistic regression analysis showed that miR-139 and miR-30b were the best diagnostic markers. The combination of miR-139 and miR-30b yielded an area under the receiver operating characteristic curve of 0.888. Additionally, serum calcium (r s  = −0.518, p < 0.001), intact parathyroid hormone (iPTH) (r s  = −0.495, p < 0.001), and alkaline phosphatase (ALP) (r s  = −0.523, p < 0.001) levels were negatively correlated with miR-30b levels.

Conclusions

miR-139, miR-222, miR-30b, miR-517c, and miR-126* were differentially expressed between PCa and PAd. The combined analysis of miR-139 and miR-30b may be used as a potential diagnostic strategy for distinguishing PCa from PAd.

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.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. C. Marcocci, F. Saponaro, Epidemiology, pathogenesis of primary hyperparathyroidism: current data. Ann. Endocrinol. 76, 113–115 (2015). https://doi.org/10.1016/j.ando.2015.03.015

    Article  Google Scholar 

  2. C. Verdelli, S. Corbetta, Epigenetic alterations in parathyroid cancers. Int. J. Mol. Sci. 18, pii: E310 (2017). https://doi.org/10.3390/ijms18020310

    Article  Google Scholar 

  3. K.M. Schulte, N. Talat, Diagnosis and management of parathyroid cancer. Nat. Rev. Endocrinol. 8, 612–622 (2012). https://doi.org/10.1038/nrendo.2012.102

    Article  CAS  PubMed  Google Scholar 

  4. A. Agarwal, R. Pradhan, N. Kumari, N. Krishnani, P. Shukla, S.K. Gupta, G. Chand, A. Mishra, G. Agarwal, A.K. Verma, S.K. Mishra, Molecular characteristics of large parathyroid adenomas. World J. Surg. 40, 607–614 (2016). https://doi.org/10.1007/s00268-015-3380-2

    Article  PubMed  Google Scholar 

  5. G. Di Leva, M. Garofalo, C.M. Croce, MicroRNAs in cancer. Annu. Rev. Pathol. 9, 287–314 (2014). https://doi.org/10.1146/annurev-pathol-012513-104715

    Article  PubMed  Google Scholar 

  6. B. Smith, P. Agarwal, N.A. Bhowmick, MicroRNA applications for prostate, ovarian and breast cancer in the era of precision medicine. Endocr. Relat. Cancer 24, R157–R172 (2017). https://doi.org/10.1530/ERC-16-0525

    Article  PubMed  PubMed Central  Google Scholar 

  7. V. Shilo, I.Z. Ben-Dov, M. Nechama, J. Silver, T. Naveh-Many, Parathyroid-specific deletion of dicer-dependent microRNAs abrogates the response of the parathyroid to acute and chronic hypocalcemia and uremia. FASEB J. 29, 3964–3976 (2015). https://doi.org/10.1096/fj.15-274191

    Article  CAS  PubMed  Google Scholar 

  8. V. Vaira, C. Verdelli, I. Forno, S. Corbetta, MicroRNAs in parathyroid physiopathology. Mol. Cell. Endocrinol. 456, 9–15 (2017). https://doi.org/10.1016/j.mce.2016.10.035

    Article  CAS  PubMed  Google Scholar 

  9. S. Corbetta, V. Vaira, V. Guarnieri, A. Scillitani, C. Eller-Vainicher, S. Ferrero, L. Vicentini, I. Chiodini, M. Bisceglia, P. Beck-Peccoz, S. Bosari, A. Spada, Differential expression of microRNAs in human parathyroid carcinomas compared with normal parathyroid tissue. Endocr. Relat. Cancer 17, 135–146 (2010). https://doi.org/10.1677/ERC-09-0134

    Article  CAS  PubMed  Google Scholar 

  10. R. Rahbari, A.K. Holloway, M. He, E. Khanafshar, O.H. Clark, E. Kebebew, Identification of differentially expressed microRNA in parathyroid tumors. Ann. Surg. Oncol. 18, 1158–1165 (2011). https://doi.org/10.1245/s10434-010-1359-7

    Article  PubMed  Google Scholar 

  11. V. Vaira, F. Elli, I. Forno, V. Guarnieri, C. Verdelli, S. Ferrero, A. Scillitani, L. Vicentini, F. Cetani, G. Mantovani, A. Spada, S. Bosari, S. Corbetta, The microRNA cluster C19MC is deregulated in parathyroid tumours. J. Mol. Endocrinol. 49, 115–124 (2012). https://doi.org/10.1530/JME-11-0189

    Article  CAS  PubMed  Google Scholar 

  12. G. Westin, Molecular genetics and epigenetics of nonfamilial (sporadic) parathyroid tumours. J. Intern. Med. 280, 551–558 (2016). https://doi.org/10.1111/joim.12458

    Article  CAS  PubMed  Google Scholar 

  13. M.I. Rather, M.N. Nagashri, S.S. Swamy, K.S. Gopinath, A. Kumar, Oncogenic microRNA-155 down-regulates tumor suppressor CDC73 and promotes oral squamous cell carcinoma cell proliferation: implications for cancer therapeutics. J. Biol. Chem. 288, 608–618 (2013). https://doi.org/10.1074/jbc.M112.425736

    Article  CAS  PubMed  Google Scholar 

  14. Z.J. Zhao, J. Shen, Circular RNA participates in the carcinogenesis and the malignant behavior of cancer. RNA Biol. 14, 514–521 (2017). https://doi.org/10.1080/15476286.2015.1122162

    Article  PubMed  Google Scholar 

  15. R.V. Lloyd, R.Y. Osamura, G. Klöppel, J. Rosai, WHO/IARC Classification of Tumours (4th edn., Volume 10) WHO Classification of Tumours of Endocrine Organs. IARC, Lyon (2017)

  16. T.D. Schmittgen, K.J. Livak, Analyzing real-time PCR data by the comparative C(t) method. Nat. Protoc. 3, 1101–1108 (2008). https://doi.org/10.1038/nprot.2008.73

    Article  CAS  PubMed  Google Scholar 

  17. D.W. Hosmer, N.L. Hjort, Goodness-of-fit processes for logistic regression: simulation results. Stat. Med. 21, 2723–2738 (2002). https://doi.org/10.1002/sim.1200

    Article  PubMed  Google Scholar 

  18. J.M. Sharretts, E. Kebebew, W.F. Simonds, Parathyroid cancer. Semin. Oncol. 37, 580–590 (2010). https://doi.org/10.1053/j.seminoncol.2010.10.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. C. Verdelli, I. Forno, V. Vaira, S. Corbetta, 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

    Article  CAS  PubMed  Google Scholar 

  20. O. Wang, C. Wang, M. Nie, Q. Cui, H. Guan, Y. Jiang, M. Li, W. Xia, X. Meng, X. Xing, Novel HRPT2/CDC73 gene mutations and loss of expression of parafibromin in Chinese patients with clinically sporadic parathyroid carcinomas. PLoS ONE 7, e45567 (2012). https://doi.org/10.1371/journal.pone.0045567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. J.D. Carpten, C.M. Robbins, A. Villablanca, L. Forsberg, S. Presciuttini, J. Bailey-Wilson, W.F. Simonds, E.M. Gillanders, A.M. Kennedy, J.D. Chen, S.K. Agarwal, R. Sood, M.P. Jones, T.Y. Moses, C. Haven, D. Petillo, P.D. Leotlela, B. Harding, D. Cameron, A.A. Pannett, A. Höög, H. Heath, L.A. James-Newton, B. Robinson, R.J. Zarbo, B.M. Cavaco, W. Wassif, N.D. Perrier, I.B. Rosen, U. Kristoffersson, P.D. Turnpenny, L.O. Farnebo, G.M. Besser, C.E. Jackson, H. Morreau, J.M. Trent, R.V. Thakker, S.J. Marx, B.T. Teh, C. Larsson, HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat. Genet. 32, 676–680 (2002). https://doi.org/10.1038/ng1048

    Article  CAS  PubMed  Google Scholar 

  22. F. Cetani, E. Pardi, C. Marcocci, Update on parathyroid carcinoma. J. Endocrinol. Invest. 39, 595–606 (2016). https://doi.org/10.1007/s40618-016-0447-3

    Article  CAS  PubMed  Google Scholar 

  23. C. Pandya, A.V. Uzilov, J. Bellizzi, C.Y. Lau, A.S. Moe, M. Strahl, W. Hamou, L.C. Newman, M.Y. Fink, Y. Antipin, W. Yu, M. Stevenson, B.M. Cavaco, B.T. Teh, R.V. Thakker, H. Morreau, E.E. Schadt, R. Sebra, S.D. Li, A. Arnold, R. Chen, Genomic profiling reveals mutational landscape in parathyroid carcinomas. JCI Insight 2, e92061 (2017). https://doi.org/10.1172/jci.insight.92061

    Article  PubMed  PubMed Central  Google Scholar 

  24. F. Cetani, C. Banti, E. Pardi, S. Borsari, P. Viacava, P. Miccoli, L. Torregrossa, F. Basolo, M.R. Pelizzo, M. Rugge, G. Pennelli, G. Gasparri, M. Papotti, M. Volante, E. Vignali, F. Saponaro, C. Marcocci, CDC73 mutational status and loss of parafibromin in the outcome of parathyroid cancer. Endocr. Connect. 2, 186–195 (2013). https://doi.org/10.1530/EC-13-0046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. M. Bacci, E. Giannoni, A. Fearns, R. Ribas, Q. Gao, M.L. Taddei, G. Pintus, M. Dowsett, C.M. Isacke, L.A. Martin, P. Chiarugi, A. Morandi, miR-155 drives metabolic reprogramming of ER+ breast cancer cells following long-term estrogen deprivation and predicts clinical response to aromatase inhibitors. Cancer Res. 76, 1615–1626 (2016). https://doi.org/10.1158/0008-5472.CAN-15-2038

    Article  CAS  PubMed  Google Scholar 

  26. C. Chen, F. Luo, X. Liu, L. Lu, H. Xu, Q. Yang, J. Xue, L. Shi, J. Li, A. Zhang, Q. Liu, NF-kB-regulated exosomal miR-155 promotes the inflammation associated with arsenite carcinogenesis. Cancer Lett. 388, 21–33 (2017). https://doi.org/10.1016/j.canlet.2016.11.027

    Article  CAS  PubMed  Google Scholar 

  27. X. Fu, H. Wen, L. Jing, Y. Yang, W. Wang, X. Liang, K. Nan, Y. Yao, T. Tian, MicroRNA-155-5p promotes hepatocellular carcinoma progression by suppressing PTEN through the PI3K/Akt pathway. Cancer Sci. 108, 620–631 (2017). https://doi.org/10.1111/cas.13177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. X.F. Zhang, R. Tu, K. Li, P. Ye, X. Cui, Tumor suppressor PTPRJ is a target of miR-155 in colorectal cancer. J. Cell. Biochem. 118, 3391–3400 (2017). https://doi.org/10.1002/jcb.25995

    Article  CAS  PubMed  Google Scholar 

  29. D.N. Gu, Q. Huang, L. Tian, The molecular mechanisms and therapeutic potential of microRNA-7 in cancer. Expert Opin. Ther. Targets 19, 415–426 (2015). https://doi.org/10.1517/14728222.2014.988708

    Article  CAS  PubMed  Google Scholar 

  30. A.R. Glover, J.T. Zhao, A.J. Gill, J. Weiss, N. Mugridge, E. Kim, A.L. Feeney, J.C. Ip, G. Reid, S. Clarke, P.S. Soon, B.G. Robinson, H. Brahmbhatt, J.A. MacDiarmid, S.B. Sidhu, MicroRNA-7 as a tumor suppressor and novel therapeutic for adrenocortical carcinoma. Oncotarget 6, 36675–36688 (2015). https://doi.org/10.18632/oncotarget.5383

    Article  PubMed  PubMed Central  Google Scholar 

  31. J.L. Horsham, C. Ganda, F.C. Kalinowski, R.A. Brown, M.R. Epis, P.J. Leedman, MicroRNA-7: a miRNA with expanding roles in development and disease. Int. J. Biochem. Cell Biol. 69, 215–224 (2015). https://doi.org/10.1016/j.biocel.2015.11.001

    Article  CAS  PubMed  Google Scholar 

  32. T.B. Hansen, J. Kjems, C.K. Damgaard, Circular RNA and miR-7 in cancer. Cancer Res. 73, 5609–5612 (2013). https://doi.org/10.1158/0008-5472.CAN-13-1568

    Article  CAS  PubMed  Google Scholar 

  33. A.M. Silva-Figueroa, N.D. Perrier, Epigenetic processes in sporadic parathyroid neoplasms. Mol. Cell. Endocrinol. (2017). https://doi.org/10.1016/j.mce.2017.04.007

  34. W. Liu, H. Li, Y. Wang, X. Zhao, Y. Guo, J. Jin, R. Chi, MiR-30b-5p functions as a tumor suppressor in cell proliferation, metastasis and epithelial-to-mesenchymal transition by targeting G-protein subunit alpha-13 in renal cell carcinoma. Gene 626, 275–281 (2017). https://doi.org/10.1016/j.gene.2017.05.040

    Article  CAS  PubMed  Google Scholar 

  35. X. Qin, J. Chen, L. Wu, Z. Liu, MiR-30b-5p acts as a tumor suppressor, repressing cell proliferation and cell cycle in human hepatocellular carcinoma. Biomed. Pharmacother. 89, 742–750 (2017). https://doi.org/10.1016/j.biopha.2017.02.062

    Article  CAS  PubMed  Google Scholar 

  36. L. Qin, H.Y. Deng, S.J. Chen, W. Wei, Y.T. Zhang, miR-139 acts as a tumor suppressor in T-cell acute lymphoblastic leukemia by targeting CX chemokine receptor 4. Am. J. Transl. Res. 9, 4059–4070 (2017)

    PubMed  PubMed Central  Google Scholar 

  37. K. Wang, J. Jin, T. Ma, H. Zhai, MiR-139-5p inhibits the tumorigenesis and progression of oral squamous carcinoma cells by targeting HOXA9. J. Cell. Mol. Med. 21, 3730–3740 (2017). https://doi.org/10.1111/jcmm.13282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. L. Ng, T.M. Wan, J.H. Man, A.K. Chow, D. Iyer, G. Chen, T.C. Yau, O.S. Lo, D.C. Foo, J.T. Poon, W.K. Leung, R.W. Pang, W.L. Law, Identification of serum miR-139-3p as a non-invasive biomarker for colorectal cancer. Oncotarget 8, 27393–27400 (2017). https://doi.org/10.18632/oncotarget.16171

    PubMed  PubMed Central  Google Scholar 

  39. H. Dai, D. Gallagher, S. Schmitt, Z.Y. Pessetto, F. Fan, A.K. Godwin, O. Tawfik, Role of miR-139 as a surrogate marker for tumor aggression in breast cancer. Hum. Pathol. 61, 68–77 (2017). https://doi.org/10.1016/j.humpath.2016.11.001

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the Peking Union Medical College Innovative Team Development Program and the Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS-I2M) (2017-I2M-1-001).

Author information

Authors and Affiliations

  1. Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China

    Ya Hu, Xiang Zhang, Ming Cui, Zhe Su, Mengyi Wang, Quan Liao & Yupei Zhao

Authors
  1. Ya Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ming Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhe Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mengyi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Quan Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yupei Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Quan Liao or Yupei Zhao.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hu, Y., Zhang, X., Cui, M. et al. Verification of candidate microRNA markers for parathyroid carcinoma. Endocrine 60, 246–254 (2018). https://doi.org/10.1007/s12020-018-1551-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-018-1551-2

Keywords

Search

Navigation