长链非编码 RNA NDRG1 通过海绵吸附 miR-96-5p 加重骨肉瘤进展并调节 PI3K/AKT 通路。
LncRNA NDRG1 aggravates osteosarcoma progression and regulates the PI3K/AKT pathway by sponging miR-96-5p.
机构信息
Department of Orthopaedics, Jinling Hospital, Nanjing Medical University, Zhongshan Road 305, Nanjing, 210002, China.
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Tianyuan East Road 818, Nanjing, 211166, China.
出版信息
BMC Cancer. 2022 Jul 4;22(1):728. doi: 10.1186/s12885-022-09833-5.
BACKGROUND
Osteosarcoma (OS) is the most common primary malignant bone tumors in children and adolescents. Large numbers of studies have focused on the long non-coding RNA (lncRNA) that plays essential roles in the progression of osteosarcoma. Nevertheless, the functions and underlying mechanisms of LncRNA NDRG1 in osteosarcoma remain unknown.
METHODS
Differentially expressed lncRNAs between osteosarcoma and adjacent normal tissues were identified through RNA sequencing. The role of LncRNA NDRG1 in osteosarcoma proliferation and metastasis were investigated through in vitro and in vivo functional experiments. The interaction between LncRNA NDRG1 and miR-96-5p was verified through bioinformatic analysis and luciferase reporter assay. Regulation relationship between LncRNA NDRG1 and miR-96-5p was further evaluated by the rescue experiments. Additionally, the changes in the expression of epithelial-mesenchymal transition (EMT) and the PI3K/AKT pathway were verified by Western blot.
RESULTS
LncRNA NDRG1 was up-regulated in osteosarcoma cell lines and tissues and the expression of LncRNA NDRG1 was correlated with the overall survival of osteosarcoma patients. Functional experiments exhibited that LncRNA NDRG1 aggravated osteosarcoma proliferation and migration in vitro; meanwhile, animals experiments showed that LncRNA NDRG1 promoted osteosarcoma growth and metastasis in vivo. Mechanistically, LncRNA NDRG1 was found to aggravate osteosarcoma progression and regulate the PI3K/AKT pathway by sponging miR-96-5p.
CONCLUSIONS
LncRNA NDRG1 aggravates osteosarcoma progression and regulates the PI3K/AKT pathway by sponging miR-96-5p. Therefore, LncRNA NDRG1 could act as a prognostic marker and a therapeutic target for osteosarcoma in the future.
背景
骨肉瘤（OS）是儿童和青少年中最常见的原发性恶性骨肿瘤。大量研究集中在长非编码 RNA（lncRNA）上，它在骨肉瘤的进展中起着至关重要的作用。然而，LncRNA NDRG1 在骨肉瘤中的功能和潜在机制尚不清楚。
方法
通过 RNA 测序鉴定骨肉瘤与相邻正常组织之间差异表达的 lncRNA。通过体外和体内功能实验研究 LncRNA NDRG1 在骨肉瘤增殖和转移中的作用。通过生物信息学分析和荧光素酶报告基因实验验证 LncRNA NDRG1 与 miR-96-5p 的相互作用。通过挽救实验进一步评估 LncRNA NDRG1 和 miR-96-5p 之间的调节关系。此外，通过 Western blot 验证上皮-间充质转化（EMT）和 PI3K/AKT 通路表达的变化。
结果
LncRNA NDRG1 在骨肉瘤细胞系和组织中上调，LncRNA NDRG1 的表达与骨肉瘤患者的总生存率相关。功能实验表明，LncRNA NDRG1 加重骨肉瘤体外增殖和迁移；同时，动物实验表明 LncRNA NDRG1 促进骨肉瘤体内生长和转移。机制上，发现 LncRNA NDRG1 通过海绵吸附 miR-96-5p 加重骨肉瘤进展并调节 PI3K/AKT 通路。
结论
LncRNA NDRG1 通过海绵吸附 miR-96-5p 加重骨肉瘤进展并调节 PI3K/AKT 通路。因此，LncRNA NDRG1 未来可能成为骨肉瘤的预后标志物和治疗靶点。
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