Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Oncol Rep. 2020 Dec;44(6):2691-2700. doi: 10.3892/or.2020.7814. Epub 2020 Oct 19.
Metastasis and chemoresistance indicate poor prognosis in patients with osteosarcoma (OS). In the present study, the expression level of microRNA(miR)‑487b‑3p in OS specimens and cell lines was found to be decreased, and the expression level of miR‑487b‑3p was associated with overall survival in patients with OS. The inhibition of miR‑487b‑3p stimulated OS cell migration and contributed to the development of chemoresistance. In contrast, the overexpression of miR‑487b‑3p significantly inhibited OS cell migration and enhanced the sensitivity of OS cells to doxorubicin treatment. In addition, the results from the present study revealed that the suppression of miR‑487b‑3p stimulates OS stemness, while the overexpression of miR‑487b‑3p suppresses OS stemness. Notably, in vivo experiments also revealed that the overexpression of miR‑487b‑3p inhibited cancer stem cell (CSC)‑induced tumor formation, and the combination treatment of miR‑487b‑3p and doxorubicin significantly inhibited CSC‑induced tumor growth. Furthermore, miR‑487b‑3p exerts its anticancer role by targeting aldehyde dehydrogenase 1 family member A3 in OS. Taken together, the results from the present study suggests that miR‑487b‑3p is a tumor suppressor and that the overexpression of miR‑487b‑3p is a novel strategy to inhibit tumor metastasis and chemoresistance in OS.
转移和化疗耐药性表明骨肉瘤（OS）患者预后不良。在本研究中，发现 miR-487b-3p 在 OS 标本和细胞系中的表达水平降低，并且 miR-487b-3p 的表达水平与 OS 患者的总生存率相关。抑制 miR-487b-3p 刺激 OS 细胞迁移，并有助于化疗耐药性的发展。相比之下，miR-487b-3p 的过表达显著抑制 OS 细胞迁移，并增强 OS 细胞对阿霉素治疗的敏感性。此外，本研究结果表明，miR-487b-3p 的抑制刺激 OS 干性，而 miR-487b-3p 的过表达抑制 OS 干性。值得注意的是，体内实验还表明，miR-487b-3p 的过表达抑制 CSC 诱导的肿瘤形成，miR-487b-3p 和阿霉素的联合治疗显著抑制 CSC 诱导的肿瘤生长。此外，miR-487b-3p 通过靶向 OS 中的醛脱氢酶 1 家族成员 A3 发挥其抗癌作用。综上所述，本研究表明 miR-487b-3p 是一种肿瘤抑制因子，miR-487b-3p 的过表达是抑制 OS 转移和化疗耐药性的一种新策略。
