Department of Medicine and Surgery, University of Parma, via A. Gramsci 14, 43126 Parma, Italy.
Department of Medicine and Surgery, University of Parma, via A. Gramsci 14, 43126 Parma, Italy; University Hospital of Parma, Parma, Italy.
Cancer Treat Res Commun. 2021;26:100276. doi: 10.1016/j.ctarc.2020.100276. Epub 2020 Dec 10.
The prognosis of patients affected by malignant pleural mesothelioma (MPM) is presently poor and no therapeutic strategies have improved their survival yet. Introduction of miRNA mimics to restore their reduced or absent functionality in cancer cells is considered an important opportunity and a combination of miR's might be even more effective. In the present study, miR-16 and miR-34a were transfected, singularly and in combination, in MPM cell lines H2052 and H28, and their effects on cell proliferation and sensitivity to cisplatin are reported. Interestingly, the overexpression of both miRs, alone or combined, slows down the cell cycle progression, modulates the p53 and HMGB1 expression and increases the sensitivity of cells to cisplatin, producing a marked impairment of cell proliferation and strengthening the apoptotic effect of the drug. However, the co-overexpression of the two miRs results more effective only in the regulation of the cell cycle, but does not enhance the sensitivity of MPM cells to cisplatin. Consequently, although the potential of miR-16 and miR-34a is confirmed, we must conclude that their combination does not improve the response of MPM to chemotherapy.
目前，患有恶性胸膜间皮瘤（MPM）的患者预后较差，尚无治疗策略能改善其生存率。将 miRNA 模拟物引入以恢复癌细胞中减少或缺失的功能被认为是一个重要的机会，miR 的组合甚至可能更有效。在本研究中，单独或联合转染 miR-16 和 miR-34a 到 MPM 细胞系 H2052 和 H28 中，并报告了它们对细胞增殖和对顺铂敏感性的影响。有趣的是，两种 miR 的过表达，单独或联合，均能减缓细胞周期进程，调节 p53 和 HMGB1 的表达，并增加细胞对顺铂的敏感性，从而显著抑制细胞增殖并增强药物的凋亡作用。然而，两种 miR 的共过表达仅在调节细胞周期方面更有效，但不能增强 MPM 细胞对顺铂的敏感性。因此，尽管证实了 miR-16 和 miR-34a 的潜力，但我们必须得出结论，它们的组合并不能改善 MPM 对化疗的反应。
