Suppressing the PI3K/AKT Pathway by miR-30d-5p Mimic Sensitizes Ovarian Cancer Cells to Cell Death Induced by High-Dose Estrogen

• Published in: Biomedicines Vol. 10; no. 9; p. 2060
• Main Authors: Varga, Alexandra, Márton, Éva, Markovics, Arnold, Penyige, András, Balogh, István, Nagy, Bálint, Szilágyi, Melinda
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 24-08-2022; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Apoptosis; Autophagy; Biomarkers; Cancer therapies; Candidates; Cell culture; Cell death; Cell growth; Cell proliferation; Enzymes; Estrogen; estrogen receptor; Estrogen receptors; Estrogens; Experiments; Gene expression; Genetic aspects; Health aspects; high-dose estrogen; Medical research; MicroRNA; MicroRNAs; miR-30; miRNA; Ovarian cancer; Tumors; United States; New York; United States > US; Germany
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines10092060

MicroRNAs are short non-coding RNA molecules that are involved in tumor development and are considered to be promising candidates in cancer therapy. Here, we studied the role of miR-30s in the pathophysiology of ovarian cancer. According to our results miR-30a-5p, miR-30d-5p, and miR-30e-5p were overexpressed in the estrogen receptor α (ERα)-expressing PEO1 cell line compared to A2780 that lacks this receptor. Furthermore, the expression of miR-30a-5p, miR-30d-5p, and miR-30e-5p were induced in response to high-dose estrogen treatment in PEO1 where intensive cell death was observed according to the induction of apoptosis and autophagy. Lacking or blocking ERα function reduced tolerance to high-dose estrogen that suggests the importance of ERα-mediated estrogen response in the maintenance of proliferation. MiR-30d-5p mimic reduced cell proliferation in both A2780 and PEO1. Furthermore, it decreased the tolerance of PEO1 cells to high-dose estrogen by blocking the ERα-mediated estrogen response. This was accompanied by decreased SOX4 expression that is thought to be involved in the regulation of the PI3K/AKT pathway. Blocking this pathway by AZD8835 led to the same results. MiR-30d-5p or AZD8835 sensitized PEO1 cells to tamoxifen. We suggest that miR-30d-5p might be a promising candidate in the therapy of ovarian cancer.