Lu Jianyi, Zhang Min, Yang Xiao, Cui Tong, Dai Jinpo
Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P.R. China.
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China.
Oncol Lett. 2017 May;13(5):3866-3872. doi: 10.3892/ol.2017.5870. Epub 2017 Mar 17.
MicroRNAs (miRNAs/miRs) are short non-coding RNAs (between 20 and 22 nucleotides) that regulate gene expression by binding to the 3'-untranslated region of target mRNA, and preventing protein translation or inducing mRNA destabilization. miRNAs are predicted to target ~60% of all mRNAs, therefore providing a marked degree of regulation of a number of cellular processes. In the present study, the expression of miR-548c-3p was determined by reverse transcription-quantitative polymerase chain reaction analysis and demonstrated to be markedly downregulated in clinical malignant glioma tissues and the glioma T98G cell line compared with normal human brain tissue. Transfection of miR-548c-3p inhibited cell proliferation by inducing G cell cycle arrest and also inhibited the migration of the T98G cells . Furthermore, a bioinformatic algorithm and a luciferase reporter assay identified proto-oncogene c-Myb (c-Myb) as a potential direct target of miR-548c-3p. Further experiments demonstrated that the inhibition of c-Myb by miR-548c-3p partially mediated the antitumor effect of miR-548c-3p. The results of the present study provide the novel insight that miR-548c-3p inhibits glioma tumorigenesis by targeting c-Myb. Therefore, miR-548c-3p may contribute to the development of improved glioma treatment.
微小RNA（miRNA/miR）是短链非编码RNA（20至22个核苷酸），通过与靶mRNA的3'非翻译区结合来调节基因表达，从而阻止蛋白质翻译或诱导mRNA不稳定。据预测，miRNA可靶向约60%的所有mRNA，因此对许多细胞过程具有显著的调控作用。在本研究中，通过逆转录-定量聚合酶链反应分析确定了miR-548c-3p的表达，结果显示与正常人类脑组织相比，其在临床恶性胶质瘤组织和胶质瘤T98G细胞系中显著下调。转染miR-548c-3p可通过诱导G期细胞周期停滞抑制细胞增殖，还可抑制T98G细胞的迁移。此外，生物信息学算法和荧光素酶报告基因检测确定原癌基因c-Myb为miR-548c-3p的潜在直接靶点。进一步实验表明，miR-548c-3p对c-Myb的抑制作用部分介导了miR-548c-3p的抗肿瘤作用。本研究结果提供了新的见解，即miR-548c-3p通过靶向c-Myb抑制胶质瘤的发生。因此，miR-548c-3p可能有助于改善胶质瘤治疗的发展。
