Department of Orthopedics, Jingzhou Hospital of Traditional Chinese Medicine, Jingzhou, China.
Jingzhou Hospital of Traditional Chinese Medicine - Functional Section, Jingzhou, China.
Braz J Med Biol Res. 2021 Jan 8;54(2):e9161. doi: 10.1590/1414-431X20209161. eCollection 2021.
Patients with osteosarcoma (OS) usually have poor overall survival because of frequent metastasis. Long non-coding RNAs (lncRNAs) have been reported to be associated with tumorigenesis and metastasis. In this study, we investigated the expression and roles of lncRNA human histocompatibility leukocyte antigen (HLA) complex P5 (HCP5) in OS, aiming to provide a novel molecular mechanism for OS. HCP5 was up-regulated both in OS tissues and cell lines and high expression of HCP5 was associated to low survival in OS patients. Down-regulation of HCP5 inhibited cell proliferation, migration, and invasion, suggesting its carcinogenic role in OS. miR-101 was targeted by HCP5 and its expression was decreased in OS. The inhibitor of miR-101 reversed the impact of HCP5 down-regulation on cell proliferation, apoptosis, and metastasis in OS. Ephrin receptor 7 (EPHA7) was proved to be a target of miR-101 and had ability to recover the effects of miR-101 inhibitor in OS. In conclusion, lncRNA HCP5 knockdown suppressed cell proliferation, migration, and invasion, and induced apoptosis through depleting the expression of EPHA7 by binding to miR-101, providing a potential therapeutic strategy of HCP5 in OS.
骨肉瘤（OS）患者的总体生存率通常较差，因为经常发生转移。长链非编码 RNA（lncRNA）已被报道与肿瘤发生和转移有关。在这项研究中，我们研究了 lncRNA 人类组织相容性白细胞抗原（HLA）复合物 P5（HCP5）在 OS 中的表达和作用，旨在为 OS 提供一种新的分子机制。HCP5 在 OS 组织和细胞系中均上调，并且 HCP5 的高表达与 OS 患者的低生存率相关。HCP5 的下调抑制了细胞增殖、迁移和侵袭，表明其在 OS 中具有致癌作用。HCP5 靶向 miR-101，并且其在 OS 中的表达降低。miR-101 抑制剂逆转了 HCP5 下调对 OS 细胞增殖、凋亡和转移的影响。Ephrin 受体 7（EPHA7）被证明是 miR-101 的靶标，并具有恢复 miR-101 抑制剂在 OS 中作用的能力。总之，lncRNA HCP5 的敲低通过与 miR-101 结合来耗尽 EPHA7 的表达，抑制细胞增殖、迁移和侵袭，并诱导凋亡，为 OS 中的 HCP5 提供了一种潜在的治疗策略。
