Open Access

Epigenetic regulation of embryonic stem cell marker miR302C in human chondrosarcoma as determinant of antiproliferative activity of proline-rich polypeptide 1

  • Authors:
    • Karina Galoian
    • Amir Qureshi
    • Gianluca D'Ippolito
    • Paul C. Schiller
    • Marco Molinari
    • Andrea L. Johnstone
    • Shaun P. Brothers
    • Ana C. Paz
    • H. T. Temple
  • View Affiliations

  • Published online on: June 18, 2015     https://doi.org/10.3892/ijo.2015.3054
  • Pages: 465-472
  • Copyright: © Galoian et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Metastatic chondrosarcoma of mesenchymal origin is the second most common bone malignancy and does not respond either to chemotherapy or radiation; therefore, the search for new therapies is relevant and urgent. We described recently that tumor growth inhibiting cytostatic proline-rich polypeptide 1, (PRP-1) significantly upregulated tumor suppressor miRNAs, downregulated onco-miRNAs in human chondrosarcoma JJ012 cell line, compared to chondrocytes culture. In this study we hypothesized the existence and regulation of a functional marker in cancer stem cells, correlated to peptides antiproliferative activity. Experimental results indicated that among significantly downregulated miRNA after PRP-1treatment was miRNAs 302c*. This miRNA is a part of the cluster miR302‑367, which is stemness regulator in human embryonic stem cells and in certain tumors, but is not expressed in adult hMSCs and normal tissues. PRP-1 had strong inhibitory effect on viability of chondrosarcoma and multilineage induced multipotent adult cells (embryonic primitive cell type). Unlike chondrosarcoma, in glioblastoma, PRP-1 does not have any inhibitory activity on cell proliferation, because in glioblastoma miR-302-367 cluster plays an opposite role, its expression is sufficient to suppress the stemness inducing properties. The observed correlation between the antiproliferative activity of PRP-1 and its action on downregulation of miR302c explains the peptides opposite effects on the upregulation of proliferation of adult mesenchymal stem cells, and the inhibition of the proliferation of human bone giant-cell tumor stromal cells, reported earlier. PRP-1 substantially downregulated the miR302c targets, the stemness markers Nanog, c-Myc and polycomb protein Bmi-1. miR302c expression is induced by JMJD2-mediated H3K9me2 demethylase activity in its promoter region. JMJD2 was reported to be a positive regulator for Nanog. Our experimental results proved that PRP-1 strongly inhibited H3K9 activity comprised of a pool of JMJD1 and JMJD2. We conclude that inhibition of H3K9 activity by PRP-1 leads to downregulation of miR302c and its targets, defining the PRP-1 antiproliferative role.
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August-2015
Volume 47 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Galoian K, Qureshi A, D'Ippolito G, Schiller PC, Molinari M, Johnstone AL, Brothers SP, Paz AC and Temple HT: Epigenetic regulation of embryonic stem cell marker miR302C in human chondrosarcoma as determinant of antiproliferative activity of proline-rich polypeptide 1. Int J Oncol 47: 465-472, 2015.
APA
Galoian, K., Qureshi, A., D'Ippolito, G., Schiller, P.C., Molinari, M., Johnstone, A.L. ... Temple, H.T. (2015). Epigenetic regulation of embryonic stem cell marker miR302C in human chondrosarcoma as determinant of antiproliferative activity of proline-rich polypeptide 1. International Journal of Oncology, 47, 465-472. https://doi.org/10.3892/ijo.2015.3054
MLA
Galoian, K., Qureshi, A., D'Ippolito, G., Schiller, P. C., Molinari, M., Johnstone, A. L., Brothers, S. P., Paz, A. C., Temple, H. T."Epigenetic regulation of embryonic stem cell marker miR302C in human chondrosarcoma as determinant of antiproliferative activity of proline-rich polypeptide 1". International Journal of Oncology 47.2 (2015): 465-472.
Chicago
Galoian, K., Qureshi, A., D'Ippolito, G., Schiller, P. C., Molinari, M., Johnstone, A. L., Brothers, S. P., Paz, A. C., Temple, H. T."Epigenetic regulation of embryonic stem cell marker miR302C in human chondrosarcoma as determinant of antiproliferative activity of proline-rich polypeptide 1". International Journal of Oncology 47, no. 2 (2015): 465-472. https://doi.org/10.3892/ijo.2015.3054