Department of Orthopedics, The Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, P.R. China.
Department of Gynecology, The Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, P.R. China.
Oncol Rep. 2018 Jun;39(6):2703-2710. doi: 10.3892/or.2018.6394. Epub 2018 Apr 23.
Osteosarcoma (OS) is the most common primary bone malignancy among children and adolescents. Deregulation of microRNAs has been well documented in OS, while the putative effects of miR‑186 have not been identified yet. In the present study, we assessed the expression of miR‑186 in a cohort of 40 OS tissues and explored its effects on OS cells. As expected, miR‑186 was suppressed in OS tissues compared with relative normal tissues. Overexpression of miR‑186 inhibited cell proliferation, arrested the cell cycle progression and suppressed the cell invasion of the HOS and U2 OS cell lines. These results indicated the tumor‑suppressive role of miR‑186 in OS. Among the target genes of miR‑186, we found that pituitary tumor transforming gene 1 (PTTG1) may be a target gene of miR‑186 in OS and that the overexpression of PTTG1 could partially abolish miR‑186‑mediated suppressive effects on OS cells. Aerobic glycolysis is the major way of energy supply and is one of the characteristic phenotypes of tumor cells. In addition, we found that overexpression of miR‑186 significantly suppressed the expression of hypoxia‑inducible factor 1 (HIF‑1) and inhibited the glucose uptake and lactate production of OS cells. Collectively, our findings demonstrated that miR‑186 functions as a tumor suppressor in OS cells partially by targeting PTTG1 and that HIF‑1‑mediated suppression of aerobic glycolysis may be also involved in its suppressive effects.
骨肉瘤(OS)是儿童和青少年中最常见的原发性骨恶性肿瘤。miRNA 的失调在 OS 中已有很好的记录,而 miR-186 的潜在作用尚未确定。在本研究中,我们评估了 miR-186 在 40 例 OS 组织中的表达,并探讨了其对 OS 细胞的影响。正如预期的那样,与相对正常组织相比,OS 组织中 miR-186 的表达受到抑制。miR-186 的过表达抑制了 HOS 和 U2 OS 细胞系的细胞增殖,使细胞周期进程停滞,并抑制了细胞侵袭。这些结果表明 miR-186 在 OS 中具有肿瘤抑制作用。在 miR-186 的靶基因中,我们发现垂体肿瘤转化基因 1(PTTG1)可能是 OS 中 miR-186 的靶基因,并且 PTTG1 的过表达可以部分消除 miR-186 对 OS 细胞的抑制作用。有氧糖酵解是能量供应的主要方式,也是肿瘤细胞的特征表型之一。此外,我们发现过表达 miR-186 显著抑制了缺氧诱导因子 1(HIF-1)的表达,并抑制了 OS 细胞的葡萄糖摄取和乳酸生成。综上所述,我们的研究结果表明,miR-186 作为 OS 细胞中的肿瘤抑制因子,部分通过靶向 PTTG1 发挥作用,而 HIF-1 介导的有氧糖酵解抑制可能也参与了其抑制作用。