miR-337-5p 通过 ERBB、MAPK 和 VEGF 通路参与骨肉瘤的发生发展。
MicroRNA-337-5p participates in the development and progression of osteosarcoma via ERBB, MAPK and VEGF pathways.
机构信息
Department of Orthopedics, The First People's Hospital of Wujiang District, Suzhou, China.
出版信息
Eur Rev Med Pharmacol Sci. 2018 Sep;22(17):5460-5470. doi: 10.26355/eurrev_201809_15806.
OBJECTIVE
To investigate the role of microRNA-337-5p in osteosarcoma (OS) and its underlying mechanism.
PATIENTS AND METHODS
The microRNA (microRNA-337-5p) that may be related to OS development was screened out by GEO (Gene Expression Omnibus) database. Survival analysis and ROC curve were performed according to microRNA-337-5p expressions in OA patients. Besides, the correlation between microRNA-337-5p expression and clinical parameters was evaluated by Chi-square analysis. Cox regression analysis was performed to detect the relationship between the overall survival and clinical parameters of OA patients. Subsequently, enriched functions and pathways of microRNA-337-5p were predicted by GESA (gene enrichment sets analysis). MicroRNA-337-5p expression was detected in 65 OS tissue samples and 30 normal tissue samples by qRT-PCR (quantitative Real-Time Polymerase Chain Reaction). For in vitro experiments, after microRNA-337-5p mimics or microRNA-337-5p inhibitor was transfected into OS cells, proliferative and invasive abilities were detected by CCK-8 (Cell Counting Kit-8) and transwell assay, respectively. Finally, Western blot was used to explore the underlying mechanism of microRNA-337-5p in regulating OS.
RESULTS
MicroRNA-337-5p was overexpressed in serum and tissue samples of OS patients, which was valuable in diagnosing OS. Besides, microRNA-337-5p expression was correlated with the overall survival and necrosis range of OA patients, whereas not correlated with age and sex. GESA indicated that microRNA-337-5p was enriched in ERBB, MAPK, and VEGF pathways. In vitro experiments indicated elevated proliferative and invasive abilities in MG63 and U2OS cells after microRNA-337-5p overexpression. Furthermore, increased expressions of ERBB2, Erk1/2, and VEGF121 were observed in OS cells after microRNA-337-5p overexpression.
CONCLUSIONS
MicroRNA-337-5p is upregulated in OS tissues, which is an independent prognostic factor in OS. Overexpressed microRNA-337-5p can promote proliferative and invasive abilities of OS cells via activating ERBB, MAPK, and VEGF pathways.
目的
探讨微小 RNA-337-5p 在骨肉瘤（OS）中的作用及其机制。
患者和方法
通过 GEO（基因表达综合数据库）数据库筛选出可能与 OS 发生发展相关的 microRNA（miR-337-5p）。根据 OA 患者 miR-337-5p 的表达进行生存分析和 ROC 曲线分析。此外，通过卡方分析评估 miR-337-5p 表达与临床参数的相关性。采用 Cox 回归分析检测 OS 患者总体生存率与临床参数的关系。随后，通过 GESA（基因富集集分析）预测 miR-337-5p 的富集功能和通路。通过 qRT-PCR（实时定量聚合酶链反应）检测 65 例 OS 组织样本和 30 例正常组织样本中的 miR-337-5p 表达。进行体外实验，转染 miR-337-5p 模拟物或 miR-337-5p 抑制剂后，通过 CCK-8（细胞计数试剂盒-8）和 Transwell 实验分别检测 OS 细胞的增殖和侵袭能力。最后，通过 Western blot 探讨 miR-337-5p 调节 OS 的潜在机制。
结果
OS 患者血清和组织样本中 miR-337-5p 表达上调，对 OS 有诊断价值。此外，miR-337-5p 表达与 OS 患者的总生存率和坏死范围相关，而与年龄和性别无关。GESA 表明，miR-337-5p 富集于 ERBB、MAPK 和 VEGF 通路。体外实验表明，miR-337-5p 过表达后，MG63 和 U2OS 细胞的增殖和侵袭能力增强。此外，miR-337-5p 过表达后 OS 细胞中 ERBB2、Erk1/2 和 VEGF121 的表达增加。
结论
miR-337-5p 在 OS 组织中上调，是 OS 的独立预后因素。过表达的 miR-337-5p 可通过激活 ERBB、MAPK 和 VEGF 通路促进 OS 细胞的增殖和侵袭能力。
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