Yang Yang, Liu Xinyu, Cheng Lulu, Li Li, Wei Zhenyu, Wang Zong, Han Gang, Wan Xuefeng, Wang Zaizhong, Zhang Jianhua, Chen Chuanliang
Henan Key Laboratory for Medical Imaging of Neurological Diseases, People's Hospital of Zhengzhou University, Zhengzhou 450003, People's Republic of China.
Department of Neurosurgery, Zhumadian Central Hospital, Zhumadian 463000, People's Republic of China.
Onco Targets Ther. 2020 Mar 13;13:2247-2260. doi: 10.2147/OTT.S232795. eCollection 2020.
Low-grade gliomas (LGG), approximately constitute one-third of all types of gliomas, are prone to relapse and metastasis. MicroRNA-138 (miR-138) is reported to be dysregulated in diverse human tumors and mainly function as a tumor suppressor. In this study, we analyzed the expression profile and function of miR-138 in LGG.
Quantitative PCR (qPCR) and public database bioinformatics analysis were performed to determine the miR-138 levels in LGG. MiR-138 overexpression in LGG cells was achieved by miR-138 mimics transfection. Cell proliferation was assessed by CCK8, EdU and colony formation assays. Cell invasion and migration were analyzed by transwell and wound-healing assays. Xenograft model was employed to study the role of miR-138 in LGG growth in vivo. The target of miR-138 was validated by multiple methods, such as luciferase reporter assay, RT-qPCR and Western blot. Bioinformatics analysis was conducted to explore the molecular mechanisms by which miR-138 contributed to LGG progression.
miR-138 was significantly downregulated in LGG tumor tissues and low expression of miR-138 was significantly associated with poor prognosis as well as relapse and metastasis in LGG patients. Functional analysis indicated that ectopic miR-138 expression suppressed LGG cell growth and invasive phenotype in vitro, and inhibited tumor development in vivo. Moreover, miR-138 directly targeted and repressed insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) by targeting the 3'-UTR of IGF2BP2, inhibiting epithelial to mesenchymal transition (EMT) to attenuate LGG aggressiveness. In addition, we found that elevated IGF2BP2 expression correlates with poor survival of LGG patients.
miR-138 may function as a tumor inhibitor by directly inhibiting IGF2BP2 and suppressing EMT in the progression of LGG.
低级别胶质瘤（LGG）约占所有类型胶质瘤的三分之一，易于复发和转移。据报道，微小RNA-138（miR-138）在多种人类肿瘤中表达失调，主要发挥肿瘤抑制作用。在本研究中，我们分析了miR-138在LGG中的表达谱及功能。
采用定量聚合酶链反应（qPCR）和公共数据库生物信息学分析来确定LGG中miR-138的水平。通过转染miR-138模拟物实现LGG细胞中miR-138的过表达。采用CCK8、EdU和集落形成试验评估细胞增殖。通过Transwell和伤口愈合试验分析细胞侵袭和迁移。采用异种移植模型研究miR-138在LGG体内生长中的作用。通过荧光素酶报告基因试验、RT-qPCR和蛋白质免疫印迹等多种方法验证miR-138的靶标。进行生物信息学分析以探索miR-138促进LGG进展的分子机制。
miR-138在LGG肿瘤组织中显著下调，miR-138低表达与LGG患者的不良预后以及复发和转移显著相关。功能分析表明，异位表达miR-138可在体外抑制LGG细胞生长和侵袭表型，并在体内抑制肿瘤发展。此外，miR-138通过靶向胰岛素样生长因子2 mRNA结合蛋白2（IGF2BP2）的3'-非翻译区直接靶向并抑制IGF2BP2，抑制上皮-间质转化（EMT）以减弱LGG的侵袭性。此外，我们发现IGF2BP2表达升高与LGG患者的不良生存相关。
miR-138可能通过直接抑制IGF2BP2并在LGG进展中抑制EMT发挥肿瘤抑制作用。
