Skip to main content
SpringerLink
Log in

Expression Profile of MiR-200 Family Members and Their Targets in Prostate Cancer

  • Published:
Cytology and Genetics Aims and scope Submit manuscript

Abstract

Background: Prostate cancer (PCa) shows the highest rate of new cancer cases in male population. Low sensitivity and specificity of traditional diagnostic tests have limited their implementation for early detection of PCa. The differential expression pattern of miR-200 family and their target genes has the potential of being considered as biomarkers for prostate cancer detection in combination with traditional screening. In this study we aimed to investigate changes in the expression profiles of the miR-200 family members/targets in PCa tissue samples. Patients and methods: We examined the miR-200 family members and their target genes (TCF7L1, CTBP2, E2F3, CTNNB1, DLC1 and EP300) expression profile using quantitative Real-time PCR (samples n = 24). Results: The results showed decreased mean expression level of miR-200a and miR-429 and DLC1 gene in tumor samples. Also, the expression level of E2F3, CTNNB1, EP300, CTBP2 and TCF7L1 genes was up-regulated in the tumor samples. ROC and AUC analysis showed that the combination of miR-200 family and their target genes expression profile successfully discriminated PCa samples from their non-tumor counterparts (miR-200 family AUC = 0.699, p < 0.01 and target genes AUC = 0.899, p < 0.0001, respectively). The results of this study indicate that the deregulated expression of the miR-200 family and their gene targets may have a role in the pathogenesis of PCa. Conclusion: We suggest further assessment of the expression profile of miR-200 family and their target genes in comparison with other PCa diagnostic biomarkers.

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

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.

Similar content being viewed by others

REFERENCES

  1. Ahmad, J., Hasnain, S.E., Siddiqui, M.A., Ahamed, M., Musarrat, J., and Al-Khedhairy, A.A., MicroRNA in carcinogenesis and cancer diagnostics: a new paradigm, Indian J. Med. Res., 2013, vol.137, no. 4, p. 680.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Alhasan, A.H., Scott, A.W., Wu, J.J., Feng, G., Meeks, J.J., Thaxton, C.S., and Mirkin, C.A., Circulating microRNA signature for the diagnosis of very high-risk prostate cancer, Proc. Natl. Acad. Sci. U. S. A., 2016, vol. 113, no. 38, pp. 10655–10660.

    Article  CAS  Google Scholar 

  3. Ambs, S., Prueitt, R.L., Yi, M., Hudson, R.S., Howe, T.M., Petrocca, F., Wallace, T.A., Liu, C.-G., Volinia, S., and Calin, G.A., Genomic profiling of microRNA and messenger RNA reveals deregulated microRNA expression in prostate cancer, Cancer Res., 2008, vol. 68, no. 15, pp. 6162–6170.

    Article  CAS  Google Scholar 

  4. Anastas, J.N. and Moon, R.T., WNT signalling pathways as therapeutic targets in cancer, Nat. Rev. Cancer, 2013, vol. 13, no. 1, p. 11.

    Article  CAS  Google Scholar 

  5. Arunkumar, G., Rao, D.M., Kuha, A., Manikandan, M., Prasanna Srinivasa Rao, H., Subbiah, S., Ilangovan, R., Murugan, A.K., and Munirajan, A.K., Dysregulation of miR-200 family microRNAs and epithelial-mesenchymal transition markers in oral squamous cell carcinoma, Oncol. Lett., 2018, vol. 15, no. 1, pp. 649–657.

    PubMed  Google Scholar 

  6. Braun, J., Hoang-Vu, C., Dralle, H., and Huttelmaier, S., Downregulation of microRNAs directs the EMT and invasive potential of anaplastic thyroid carcinomas, Oncogene, 2010, vol. 29, no. 29, pp. 4237–4244.

    Article  CAS  Google Scholar 

  7. Carter, J.V., Pan, J., Rai, S.N., and Galandiuk, S., ROC-ing along: evaluation and interpretation of receiver operating characteristic curves, Surgery, 2016, vol. 159, no. 6, pp. 1638–1645.

    Article  Google Scholar 

  8. Cary, K.C. and Cooperberg, M.R., Biomarkers in prostate cancer surveillance and screening: past, present, and future, Ther. Adv. Urol., 2013, vol. 5, no. 6, pp. 318–329.

    Article  CAS  Google Scholar 

  9. da Silva, H.B., Amaral, E.P., Nolasco, E.L., de Victo, N.C., Atique, R., Jank, C.C., Anschau, V., Zerbini, L.F., and Correa, R.G., Dissecting major signaling pathways throughout the development of prostate cancer, Prostate Cancer, 2013.

  10. Feng, X., Wang, Z., Fillmore, R., and Xi, Y., MiR-200, a new star miRNA in human cancer, Cancer Lett., 2014, vol. 344, no. 2, pp. 166–173.

    Article  CAS  Google Scholar 

  11. Filella, X. and Foj, L., miRNAs as novel biomarkers in the management of prostate cancer, Clin. Chem. Lab. Med., 2017, vol. 55, no. 5, pp. 715–736. https://doi.org/10.1515/cclm-2015-1073

    Article  CAS  PubMed  Google Scholar 

  12. Foster, C.S., Falconer, A., Dodson, A.R., Norman, A.R., Dennis, N., Fletcher, A., Southgate, C., Dowe, A., Dearnaley, D., and Jhavar, S., Transcription factor E2F3 overexpressed in prostate cancer independently predicts clinical outcome, Oncogene, 2004, vol. 23, no. 35, pp. 5871–5879.

    Article  CAS  Google Scholar 

  13. Ghahhari, N.M. and Babashah, S., Interplay between microRNAs and WNT/β-catenin signalling pathway regulates epithelial–mesenchymal transition in cancer, Eur. J. Cancer, 2015, vol. 51, no. 12, pp. 1638–1649.

    Article  CAS  Google Scholar 

  14. Groskopf, J., Aubin, S.M., Deras, I.L., Blase, A., Bodrug, S., Clark, C., Brentano, S., Mathis, J., Pham, J., and Meyer, T., APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer, Clin. Chem., 2006, vol. 52, no. 6, pp. 1089–1095.

    Article  CAS  Google Scholar 

  15. Guan, M., Zhou, X., Soulitzis, N., Spandidos, D.A., and Popescu, N.C., Aberrant methylation and deacetylation of deleted in liver cancer-1 gene in prostate cancer: potential clinical applications, Clin. Cancer Res., 2006, vol. 12, no. 5, pp. 1412–1419.

    Article  CAS  Google Scholar 

  16. Haldrup, C., Kosaka, N., Ochiya, T., Borre, M., Hoyer, S., Orntoft, T.F., and Sorensen, K.D., Profiling of circulating microRNAs for prostate cancer biomarker discovery, Drug Deliv. Transl. Res., 2014, vol. 4, no. 1, pp. 19–30.

    Article  CAS  Google Scholar 

  17. Humphries, B. and Yang, C., The microRNA-200 family: small molecules with novel roles in cancer development, progression and therapy, Oncotarget, 2015, vol. 6, no. 9, p. 6472.

    Article  Google Scholar 

  18. Jaiswal, S., Sarmad, R., Arora, S., Dasaraju, R., and Sarmad, K., Prostate cancer for the internist, N. Am. J. Med. Sci., 2015, vol. 7, no. 10, p. 429.

    Article  Google Scholar 

  19. Khorasani, M., Teimoori-Toolabi, L., Farivar, T.N., Asgari, M., Abolhasani, M., Shahrokh, H., Afgar, A., Kalantari, E., Peymani, A., and Mahdian, R., Aberrant expression of miR-141 and nuclear receptor small heterodimer partner in clinical samples of prostate cancer, Cancer Biomark, 2018, vol. 22, no. 1, pp. 19–28. https://doi.org/10.3233/cbm-170696

    Article  CAS  PubMed  Google Scholar 

  20. Koutsaki, M., Libra, M., Spandidos, D.A., and Zaravinos, A., The miR-200 family in ovarian cancer, Oncotarget, 2017, vol. 8, no. 39, p. 66629.

    Article  Google Scholar 

  21. Leone, G., DeGregori, J., Yan, Z., Jakoi, L., Ishida, S., Williams, R.S., and Nevins, J.R., E2F3 activity is regulated during the cell cycle and is required for the induction of S phase, Genes Dev., 1998, vol. 12, no. 14, pp. 2120–2130.

    Article  CAS  Google Scholar 

  22. Maierthaler, M., Benner, A., Hoffmeister, M., Surowy, H., Jansen, L., Knebel, P., Chang-Claude, J., Brenner, H., and Burwinkel, B., Plasma miR-122 and miR-200 family are prognostic markers in colorectal cancer, Int. J. Cancer, 2017, vol. 140, no. 1, pp. 176–187.

    Article  CAS  Google Scholar 

  23. McDermott, J.E., Wang, J., Mitchell, H., Webb-Robertson, B.-J., Hafen, R., Ramey, J., and Rodland, K.D., Challenges in biomarker discovery: combining expert insights with statistical analysis of complex omics data, Expert Opin. Med. Diagn., 2013, vol. 7, no. 1, pp. 37–51.

    Article  CAS  Google Scholar 

  24. Murata, T., Takayama, K., Katayama, S., Urano, T., Horie-Inoue, K., Ikeda, K., Takahashi, S., Kawazu, C., Hasegawa, A., and Ouchi, Y., miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression, Prostate Cancer Prostat. Dis., 2010, vol. 13, no. 4, p. 356.

    Article  CAS  Google Scholar 

  25. Nakazawa, M. and Kyprianou, N., Epithelial-mesenchymal-transition regulators in prostate cancer: androgens and beyond, J. Steroid Biochem. Mol. Biol., 2017, vol. 166, pp. 84–90.

    Article  CAS  Google Scholar 

  26. Ozen, M., Creighton, C., Ozdemir, M., and Ittmann, M., Widespread deregulation of microRNA expression in human prostate cancer, Oncogene, 2008, vol. 27, no. 12, p. 1788.

    Article  CAS  Google Scholar 

  27. Pendlebury, A., Hannan, N.J., Binder, N., Beard, S., Mcgauran, M., Grant, P., Tong, S., and Whitehead, C.L., The circulating microRNA-200 family in whole blood are potential biomarkers for high-grade serous epithelial ovarian cancer, Biomed. Rep., 2017, vol. 6, no. 3, pp. 319–322.

    Article  CAS  Google Scholar 

  28. Rice, K.R., Chen, Y., Ali, A., Whitman, E.J., Blase, A., Ibrahim, M., Elsamanoudi, S., Brassell, S., Furusato, B., and Stingle, N., Evaluation of the ETS-related gene mRNA in urine for the detection of prostate cancer, Clin. Cancer Res., 2010, pp. 1078–0432. CCR-1009-2191.

  29. Saini, S., PSA and beyond: alternative prostate cancer biomarkers, Cell. Oncol., 2016, vol. 39, no. 2, pp. 97–106.

    Article  CAS  Google Scholar 

  30. Schaefer, A., Jung, M., Miller, K., Lein, M., Kristiansen, G., Erbersdobler, A., and Jung, K., Suitable reference genes for relative quantification of miRNA expression in prostate cancer, Exp. Mol. Med., 2010, vol. 42, no. 11, pp. 749–758.

    Article  CAS  Google Scholar 

  31. Shahbazi, S., Khorasani, M., and Mahdian, R., Gene expression profile of FVII and AR in primary prostate cancer, Cancer Biomarkers, 2016, vol. 17 (3):353-358.

    Article  CAS  Google Scholar 

  32. Siegel, R.L., Miller, K.D., and Jemal, A., Cancer Statistics, 2017, CA Cancer J. Clin., 2017, vol. 67, no. 1, pp. 7–30. https://doi.org/10.3322/caac.21387

    Article  Google Scholar 

  33. Szczyrba, J., Löprich, E., Wach, S., Jung, V., Unteregger, G., Barth, S., Grobholz, R., Wieland, W., Stöhr, R., and Hartmann, A., The microRNA profile of prostate carcinoma obtained by deep sequencing, Mol. Cancer Res., 2010, pp. 1541–7786. MCR-1509-0443.

  34. Tripathi, V., Popescu, N.C., and Zimonjic, D.B., DLC1 suppresses NF-kB activity in prostate cancer cells due to its stabilizing effect on adherens junctions, SpringerPlus, 2014, vol. 3, no. 1, p. 27.

    Article  Google Scholar 

  35. Watahiki, A., Macfarlane, R.J., Gleave, M.E., Crea, F., Wang, Y., Helgason, C.D., and Chi, K.N., Plasma miRNAs as biomarkers to identify patients with castration-resistant metastatic prostate cancer, Int. J. Mol. Sci., 2013, vol. 14, no. 4, pp. 7757–7770.

    Article  Google Scholar 

  36. Wei, J., Gao, W., Zhu, C.-J., Liu, Y.-Q., Mei, Z., Cheng, T., and Shu, Y.-Q., Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer, Chin. J. Cancer, 2011, vol. 30, no. 6, p. 407.

    Article  CAS  Google Scholar 

  37. Wiklund, E.D., Bramsen, J.B., Hulf, T., Dyrskjot, L., Ramanathan, R., Hansen, T.B., Villadsen, S.B., Gao, S., Ostenfeld, M.S., and Borre, M., Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer, Int. J. Cancer, 2011, vol. 128, no. 6, pp. 1327–1334.

    Article  CAS  Google Scholar 

  38. Williams, L.V., Veliceasa, D., Vinokour, E., and Volpert, O.V., miR-200b inhibits prostate cancer EMT, growth and metastasis, PLoS One, 2013, vol. 8, no. 12, e83991.

    Article  Google Scholar 

  39. Xu, G., Wu, J., Zhou, L., Chen, B., Sun, Z., Zhao, F., and Tao, Z., Characterization of the small RNA transcriptomes of androgen dependent and independent prostate cancer cell line by deep sequencing, PLoS One, 2010, vol. 5, no. 11, e15519.

    Article  CAS  Google Scholar 

  40. Yam, J.W.P., Tse, E.Y.T., and Ng, I.O.L., Role and significance of focal adhesion proteins in hepatocellular carcinoma, J. Gastroenterol. Hepatol., 2009, vol. 24, no. 4, pp. 520–530.

    Article  CAS  Google Scholar 

  41. Zhu, W., He, J., Chen, D., Zhang, B., Xu, L., Ma, H., Liu, X., Zhang, Y., and Le, H., Expression of miR-29c, miR-93, and miR-429 as potential biomarkers for detection of early stage non-small lung cancer, PLoS One, 2014, vol. 9, no. 2, e87780.

    Article  Google Scholar 

  42. Zidar, N., Boštjančič, E., Gale, N., Kojc, N., Poljak, M., Glavač, D., and Cardesa, A., Down-regulation of microRNAs of the miR-200 family and miR-205, and an altered expression of classic and desmosomal cadherins in spindle cell carcinoma of the head and neck—hallmark of epithelial-mesenchymal transition, Hum. Pathol., 2011, vol. 42, no. 4, pp. 482–488.

    Article  CAS  Google Scholar 

Download references

ACKNOWLEDGMENTS

The authors would like to thank Dr. M. Asgari at the Oncopathology Research Center for kindly organizing this multi-centric study.

Funding

This study was supported by the Pasteur Institute of Iran (grant no. 825).

Author information

Authors and Affiliations

  1. Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

    Maryam Khorasani & Reza Mahdian

  2. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Shirin Shahbazi

  3. Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran

    Maryam Abolhasani

  4. Department of Pathology, Hasheminejad Kidney Center, Iran University of Medical Sciences, Tehran, Iran

    Maryam Abolhasani

  5. Department of Uro-Oncology, Hasheminejad Kidney Center, Iran University of Medical Sciences, Tehran, Iran

    Hossein Shahrokh

Authors
  1. Maryam Khorasani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shirin Shahbazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maryam Abolhasani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hossein Shahrokh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Reza Mahdian
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Reza Mahdian.

Ethics declarations

Conflict of interest. The authors declare that they have no conflict of interest.

Statement of compliance with standards of research involving humans as subjects. This study was approved by the Research Ethics Committee of the Pasteur Institute of Iran. Each patient signed a written informed consent form approved by the Ethics Committee of the Research Center.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maryam Khorasani, Shahbazi, S., Abolhasani, M. et al. Expression Profile of MiR-200 Family Members and Their Targets in Prostate Cancer. Cytol. Genet. 55, 357–367 (2021). https://doi.org/10.3103/S009545272104006X

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.3103/S009545272104006X

Keywords:

Search

Navigation