Department of Radiation Oncology, Tianjin Medical University General Hospital, Tianjin, 300052, China.
2Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China; 3Tianjin Neurological Institute, Tianjin, 300052, China.
Acta Biochim Pol. 2022 Mar 2;69(1):147-153. doi: 10.18388/abp.2020_5777.
The microRNA-151 (miR-151) has been reported to be involved in the growth, development, and tumorigenesis of different types of human cancers. This study was designed to unravel the role and therapeutic potential of miR-151 in glioma. The results showed glioma was found to be associated with significant (P<0.05) downregulation of miR-151. Low expression of miR-151 was also associated with poor survival of the glioma patients. Overexpression of miR-151 resulted in a significant (P<0.05) decline of glioma cell proliferation and colony formation. The sensitivity of the glioma cells to adriamycin also increased significantly (P<0.05) upon miR-151 overexpression. Additionally, overexpression of miR-151 also suppressed the migration and invasion of the human glioma cells. This was also associated with alteration in the expression of epithelial mesenchymal transition proteins. The expression of E-cadherin was increased while as that of N-cadherin, vimentin, and Snail was considerably decreased upon miR-151 overexpression. Bioinformatic analysis and ducal luciferase assay showed miR-151 targets profilin 2 (PFN2) in human glioma cells. The expression of PFN2 was found to be significantly (P<0.05) upregulated in human glioma tissues cells and cell lines. Nonetheless, the PFN2 expression was considerably suppressed upon miR-151 overexpression. Knockdown of PFN2 resulted in decrease of glioma cells proliferation. In contrary, overexpression of PFN2 could avoid the tumor-suppressive effects of miR-151. Taken together, present study points towards the tumor-suppressive effects of miR-151 and prospective therapeutic implications in human glioma.
miR-151 在不同类型的人类癌症的生长、发育和肿瘤发生中起作用。本研究旨在揭示 miR-151 在神经胶质瘤中的作用和治疗潜力。结果表明，miR-151 的表达与神经胶质瘤显著相关（P<0.05）下调。miR-151 表达水平低与神经胶质瘤患者的生存不良相关。miR-151 的过表达导致神经胶质瘤细胞增殖和集落形成显著（P<0.05）下降。miR-151 过表达也显著（P<0.05）增加了神经胶质瘤细胞对阿霉素的敏感性。此外，miR-151 的过表达还抑制了人神经胶质瘤细胞的迁移和侵袭。这也与上皮间质转化蛋白表达的改变有关。E-钙黏蛋白的表达增加，而 N-钙黏蛋白、波形蛋白和 Snail 的表达则在 miR-151 过表达时显著降低。生物信息学分析和双荧光素酶报告基因检测显示，miR-151 靶向人神经胶质瘤细胞中的原肌球蛋白 2（PFN2）。在人神经胶质瘤组织细胞和细胞系中发现 PFN2 的表达显著（P<0.05）上调。然而，miR-151 过表达时 PFN2 的表达明显受到抑制。PFN2 的敲低导致神经胶质瘤细胞增殖减少。相反，PFN2 的过表达可以避免 miR-151 的肿瘤抑制作用。总之，本研究表明 miR-151 具有肿瘤抑制作用，并可能对人类神经胶质瘤具有潜在的治疗意义。
