Involvement of let-7/miR-98 microRNAs in the regulation of progesterone receptor membrane component 1 expression in ovarian cancer cells

  • Authors:
    • Alexandra Wendler
    • Daniela Keller
    • Christian Albrecht
    • John J. Peluso
    • Martin Wehling
  • View Affiliations

  • Published online on: January 1, 2011     https://doi.org/10.3892/or_00001071
  • Pages: 273-279
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Abstract

PGRMC1 (progesterone receptor membrane component 1) is part of a multi-protein complex, that is highly expressed in several cancers and is involved in chemoresistance. Although PGRMC1 plays an important role in various cancers, little is known about how PGRMC1 expression is regulated. Therefore, the present study was designed to elucidate the molecular mechanisms that influence PGRMC1 expression in ovarian cancer cells. An in silico approach revealed that the 3'-untranslated region of PGRMC1 contains one highly and one poorly conserved binding site for the microRNA let-7/miR-98 and one highly conserved binding site for miR-141/200a. Luciferase assays and real-time PCRs showed that the let-7 isoforms let-7i and miR-98 target PGRMC1 in SKOV-3 cells. In contrast, the conserved binding site for miR-200a/141 in the 3'-UTR of PGRMC1 is not functional. Stimulation of SKOV-3 cells with progesterone resulted in a decrease in PGRMC1 mRNA levels. Further, an analysis of endogenous let-7i levels in SKOV-3 cells revealed that let-7i expression increased after stimulation with progesterone. Therefore, progesterone may exert its effect on PGRMC1 expression in part by stimulation of let-7i. In conclusion, we propose that PGRMC1 expression is regulated by the miRNAs let-7/miR-98, which could become therapeutic targets, as PGRMC1, like many other targets of let-7, seems to be involved in cancer proliferation and chemotherapy resistance.

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January 2011
Volume 25 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Wendler A, Keller D, Albrecht C, Peluso JJ and Wehling M: Involvement of let-7/miR-98 microRNAs in the regulation of progesterone receptor membrane component 1 expression in ovarian cancer cells . Oncol Rep 25: 273-279, 2011
APA
Wendler, A., Keller, D., Albrecht, C., Peluso, J.J., & Wehling, M. (2011). Involvement of let-7/miR-98 microRNAs in the regulation of progesterone receptor membrane component 1 expression in ovarian cancer cells . Oncology Reports, 25, 273-279. https://doi.org/10.3892/or_00001071
MLA
Wendler, A., Keller, D., Albrecht, C., Peluso, J. J., Wehling, M."Involvement of let-7/miR-98 microRNAs in the regulation of progesterone receptor membrane component 1 expression in ovarian cancer cells ". Oncology Reports 25.1 (2011): 273-279.
Chicago
Wendler, A., Keller, D., Albrecht, C., Peluso, J. J., Wehling, M."Involvement of let-7/miR-98 microRNAs in the regulation of progesterone receptor membrane component 1 expression in ovarian cancer cells ". Oncology Reports 25, no. 1 (2011): 273-279. https://doi.org/10.3892/or_00001071