Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, P.R. China.
Oncol Rep. 2013 Nov;30(5):2111-8. doi: 10.3892/or.2013.2685. Epub 2013 Aug 22.
microRNAs (miRNAs) are short noncoding RNAs, which modulate the expression of numerous genes by targeting mRNAs. Numerous abnormal miRNA expression patterns are found in various human malignancies, and certain miRNAs act as oncogenes or tumor suppressors. microRNA-155 (miR‑155) may not only function as an oncogene but also as a tumor suppressor in various types of cancer cells, such as melanoma. Although miR-155 has been found to be upregulated in glioma, its role has not yet been eludicated in glioma tumorigenesis. Based on the prediction of the target genes of miR-155, we hypothesized that there is a significant association between miR-155 and FOXO3a, a negative regulator of Akt signaling. In the present study, we found that FOXO3a expression was significantly downregulated and miR-155 was upregulated in a panel of glioma cells and tissue specimens. Furthermore, we demonstrated that miR-155 induced cell proliferation by inhibiting apoptosis and promoted the migration and invasiveness of glioma cells, while miR-155 had no effect on the cell cycle as determined by gain-of-function and loss-of-function experiments. Moreover, we confirmed that miR-155 downregulated the expression of FOXO3a by directly targeting its 3'-UTR. These findings indicate that miR-155 may function as an oncogene by targeting FOXO3a in the development and progression of glioma.
microRNAs (miRNAs) 是短的非编码 RNA,可以通过靶向 mRNAs 来调节许多基因的表达。在各种人类恶性肿瘤中发现了许多异常的 miRNA 表达模式,某些 miRNA 作为癌基因或肿瘤抑制因子发挥作用。miRNA-155 (miR-155) 不仅可以作为癌基因,也可以作为各种类型癌细胞(如黑色素瘤)中的肿瘤抑制因子。虽然已经发现 miR-155 在神经胶质瘤中上调,但它在神经胶质瘤发生中的作用尚未阐明。基于 miR-155 靶基因的预测,我们假设 miR-155 与 Akt 信号的负调节剂 FOXO3a 之间存在显著关联。在本研究中,我们发现 miR-155 在一组神经胶质瘤细胞和组织标本中表达显著上调,而 FOXO3a 表达显著下调。此外,我们证明 miR-155 通过抑制细胞凋亡诱导细胞增殖,并促进神经胶质瘤细胞的迁移和侵袭,而 miR-155 对细胞周期没有影响,这是通过功能获得和功能丧失实验确定的。此外,我们证实 miR-155 通过直接靶向其 3'-UTR 下调 FOXO3a 的表达。这些发现表明,miR-155 可能通过靶向 FOXO3a 在神经胶质瘤的发生和发展中发挥癌基因的作用。