Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología‑Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
Oncogenomics Laboratory, The National Institute of Genomic Medicine, Mexico City 14610, Mexico.
Mol Med Rep. 2021 Jun;23(6). doi: 10.3892/mmr.2021.12114. Epub 2021 Apr 26.
Glioblastomas (GBMs) are the most frequent and malignant type of brain tumor. It has been reported that progesterone (P4) regulates the progression of GBMs by modifying the expression of genes that promote cell proliferation, migration and invasion; however, it is not fully understood how these processes are regulated. It is possible that P4 mediates some of these effects through changes in the microRNA (miRNA) expression profile in GBM cells. The present study investigated the effects of P4 on miRNAs expression profile in U‑251MG cells derived from a human GBM. U‑251MG cells were treated for 6 h with P4, RU486 (an antagonist of the intracellular progesterone receptor), the combined treatment (P4+RU486) and cyclodextrin (vehicle) and then a miRNA microarray analysis conducted. The expression analysis revealed a set of 190 miRNAs with differential expression in the treatments of P4, RU486 and P4+RU486 in respect to the vehicle and P4 in respect to P4+RU486, of which only 16 were exclusively regulated by P4. The possible mRNA targets of the miRNAs regulated by P4 could participate in the regulation of proliferation, cell cycle progression and cell migration of GBMs. The present study provided insight for understanding epigenetic modifications regulated by sex hormones involved in GBM progression, and for identifying potential therapeutic strategies for these brain tumors.
胶质母细胞瘤(GBM)是最常见和恶性程度最高的脑肿瘤。有报道称,孕激素(P4)通过调节促进细胞增殖、迁移和侵袭的基因表达来调控 GBM 的进展;然而,这些过程是如何被调控的还不完全清楚。P4 可能通过改变 GBM 细胞中的 microRNA(miRNA)表达谱来介导其中一些作用。本研究探讨了 P4 对源自人 GBM 的 U-251MG 细胞中 miRNA 表达谱的影响。用 P4、RU486(细胞内孕激素受体的拮抗剂)、联合处理(P4+RU486)和环糊精(载体)处理 U-251MG 细胞 6 小时,然后进行 miRNA 微阵列分析。表达分析显示,在 P4、RU486 和 P4+RU486 处理与载体以及 P4 处理与 P4+RU486 处理相比,有 190 个 miRNA 的表达存在差异,其中只有 16 个 miRNA 仅受 P4 调控。受 P4 调控的 miRNA 的可能 mRNA 靶标可能参与 GBM 的增殖、细胞周期进程和细胞迁移的调控。本研究为了解涉及 GBM 进展的性激素的表观遗传修饰提供了深入的认识,并为这些脑肿瘤确定了潜在的治疗策略。