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Altered expression of mir-222 and mir-25 influences diverse gene expression changes in transformed normal and anaplastic thyroid cells, and impacts on MEK and TRAIL protein expression

  • Authors:
    • Sinéad T. Aherne
    • Paul Smyth
    • Michael Freeley
    • Leila Smith
    • Cathy Spillane
    • John O'Leary
    • Orla Sheils

  • View Affiliations

  • Published online on: June 22, 2016     https://doi.org/10.3892/ijmm.2016.2653
  • Pages: 433-445

  • Copyright: © Aherne et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Thyroid cancer is the most common endocrine malignancy and accounts for the majority of endocrine cancer-related deaths each year. Our group and others have previously demonstrated dysfunctional microRNA (miRNA or miR) expression in the context of thyroid cancer. The objective of the present study was to investigate the impact of synthetic manipulation of expression of miR-25 and miR-222 in benign and malignant thyroid cells. miR-25 and miR-222 expression was upregulated in 8505C (an anaplastic thyroid cell line) and Nthy-ori (a SV40-immortalised thyroid cell line) cells, respectively. A transcriptomics-based approach was utilised to identify targets of the two miRNAs and real-time PCR and western blotting were used to validate a subset of the targets. Almost 100 mRNAs of diverse functions were found to be either directly or indirectly targeted by both miR-222 and miR-25 [fold change ≥2, false discovery rate (FDR) ≤0.05]. Gene ontology analysis showed the miR-25 gene target list to be significantly enriched for genes involved in cell adhesion. Fluidigm real-time PCR technologies were used to validate the downregulation of 23 and 22 genes in response to miR-25 and miR-222 overexpression, respectively. The reduction of the expression of two miR-25 protein targets, TNF-related apoptosis‑inducing ligand (TRAIL) and mitogen-activated protein kinase kinase 4 (MEK4), was also validated. Manipulating the expression of both miR-222 and miR-25 influenced diverse gene expression changes in thyroid cells. Increased expression of miR-25 reduced MEK4 and TRAIL protein expression, and cell adhesion and apoptosis are important aspects of miR-25 functioning in thyroid cells.
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August-2016
Volume 38 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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  • Ranked Medicine Research and Experimental
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  • CiteScore: 10.7
  • CiteScore Rank: Q1: #35/328 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 0.994
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Spandidos Publications style
Aherne ST, Smyth P, Freeley M, Smith L, Spillane C, O'Leary J and Sheils O: Altered expression of mir-222 and mir-25 influences diverse gene expression changes in transformed normal and anaplastic thyroid cells, and impacts on MEK and TRAIL protein expression. Int J Mol Med 38: 433-445, 2016
APA
Aherne, S.T., Smyth, P., Freeley, M., Smith, L., Spillane, C., O'Leary, J., & Sheils, O. (2016). Altered expression of mir-222 and mir-25 influences diverse gene expression changes in transformed normal and anaplastic thyroid cells, and impacts on MEK and TRAIL protein expression. International Journal of Molecular Medicine, 38, 433-445. https://doi.org/10.3892/ijmm.2016.2653
MLA
Aherne, S. T., Smyth, P., Freeley, M., Smith, L., Spillane, C., O'Leary, J., Sheils, O."Altered expression of mir-222 and mir-25 influences diverse gene expression changes in transformed normal and anaplastic thyroid cells, and impacts on MEK and TRAIL protein expression". International Journal of Molecular Medicine 38.2 (2016): 433-445.
Chicago
Aherne, S. T., Smyth, P., Freeley, M., Smith, L., Spillane, C., O'Leary, J., Sheils, O."Altered expression of mir-222 and mir-25 influences diverse gene expression changes in transformed normal and anaplastic thyroid cells, and impacts on MEK and TRAIL protein expression". International Journal of Molecular Medicine 38, no. 2 (2016): 433-445. https://doi.org/10.3892/ijmm.2016.2653