Zhang Jingwei, Zhang Jieyuan, Zhang Dong, Ni Weifeng, Xiao Haijun, Zhao Bizeng
Department of Orthopedics, Shanghai Fengxian District Central Hospital/Southern Medical University Affiliated Fengxian Hospital, No. 6600 Nanfeng Road, Shanghai, 201499, China.
Department of Orthopedics, Shanghai Sixth People's Hospital, No. 600 Yishan Road, Shanghai, 200233, China.
Cancer Cell Int. 2020 Mar 30;20:100. doi: 10.1186/s12935-020-01170-6. eCollection 2020.
Osteosarcoma (OS) is one of the most common types of primary bone tumors which poses negative effects on the bones of both young children and adolescents. LncRNA LINC00472 has been reported to be involved with poor prognostics in breast cancer and ovarian cancer. As a new lncRNA, its role in OS remains to be elusive. Herein, we are focused to explore its regulatory mechanism in the development of OS.
qRT-PCR was utilized to examine the expressions of LINC00472 and miR-300 in OS tissues and cell lines. OS cell lines of U2OS and MG63 were used to investigate the biological function of LINC00472. Xenograft tumor model was built in nude mice with MG63 cells.
The expressions of LINC00472 were inhibited in OS tissues and cells, and were negatively related to the expressions of miR-300. LINC00472 directly targeted miR-300. FOXO1 was inhibited in OS tissues and its expressions were negatively related to the expressions of miR-300. LINC00472 over-expressions decreased cell proliferation abilities and colony formation abilities. These effects were mediated by miR-300. The silence of LINC00472 and over-expressions of miR-300 suppressed FOXO1 expressions. LINC00472 greatly reduced tumor growth in vivo and this effect was attenuated by miR-300 mimic.
From all the experiments and observations, we demonstrated that LINC00472 could be a potential tumor suppressor in OS through interacting with miR-300 and FOXO1.
骨肉瘤（OS）是最常见的原发性骨肿瘤类型之一，对幼儿和青少年的骨骼均有负面影响。据报道，长链非编码RNA LINC00472与乳腺癌和卵巢癌的不良预后有关。作为一种新的长链非编码RNA，其在骨肉瘤中的作用仍不明确。在此，我们致力于探索其在骨肉瘤发生发展中的调控机制。
采用qRT-PCR检测骨肉瘤组织和细胞系中LINC00472和miR-300的表达。利用U2OS和MG63骨肉瘤细胞系研究LINC00472的生物学功能。将MG63细胞接种于裸鼠建立异种移植瘤模型。
LINC00472在骨肉瘤组织和细胞中的表达受到抑制，且与miR-300的表达呈负相关。LINC00472直接靶向miR-300。FOXO1在骨肉瘤组织中的表达受到抑制，其表达与miR-300的表达呈负相关。LINC00472过表达降低了细胞增殖能力和集落形成能力。这些作用是由miR-300介导的。LINC00472沉默和miR-300过表达抑制了FOXO1的表达。LINC00472显著降低了体内肿瘤的生长，而miR-300模拟物可减弱这种作用。
通过所有实验和观察，我们证明LINC00472可能通过与miR-300和FOXO1相互作用成为骨肉瘤潜在的肿瘤抑制因子。
