Abstract. MicroRNA (miR)-27b has been reported to participate in glioma. However, a detailed role of miR-27b and the underlying mechanism remain largely unknown. The present study found that the expression of miR-27b was significantly increased in glioma tissues compared with normal adjacent tissues. In addition, miR-27b was also upregulated in the U87, U251 and SHG44 glioma cell lines compared with normal human astrocytes. Sprouty homolog 2 (Spry2), which has been reported to be associated with invasive glioma, was identified as a novel target of miR-27b in U251 glioma cells, and the protein expression of Spry2 was negatively regulated by miR-27b in U251 cells. Additionally, inhibition of miR-27b and upregulation of Spry2 suppressed glioma cell invasion, while downregulation of Spry2 reversed the suppressive effect of miR-27b inhibition on glioma cell invasion. These data suggest that miR-27b may promote glioma cell invasion through direct inhibition of Spry2 expression. The data also suggest that miR-27b may become a promising molecular target for inhibiting the invasion and metastasis of glioma.
IntroductionGlioma is among the most common human malignancies in the brain. Although the five-year survival rate of patients with glioma has been improved in recent years due to the combination of surgery, radiotherapy and chemotherapy, the prognosis of patients with invasive glioma remains poor (1,2). It has been demonstrated that dysfunction of oncogenes or tumor suppressors is closely associated with the development and progression of glioma (2). Accordingly, developing novel molecular targets may be promising for the development of therapeutic strategies for invasive glioma.MicroRNAs (miRNAs), a class of non-coding RNAs 18-25 nucleotides in length, can induce mRNA degradation or suppress protein translation by binding to the seed sequences in the 3'-untranslational region (UTR) of mRNAs. By negatively regulating the protein expression of their targets, microRNAs exert adverse effects on cell survival, proliferation and motility (3). Dysfunctions of miRNAs, which act as oncogenes or tumor suppressors, have been demonstrated to be associated with human malignancies (4). Furthermore, deregulations of numerous miRNAs have been revealed to contribute to the development and progression of invasive glioma, including miRNA-20a (miR-20a), miR-106a, miR-145, miR-494 and miR-124 (5-8). MiR-27b has been reported to be associated with glioma (9). However, the detailed role of miR-27b in the regulation of invasive glioma remains largely unknown.Sprouty homolog 2 (Spry2), a member of the sprouty family, contains a carboxyl-terminal cysteine-rich domain essential for the inhibition of receptor tyrosine kinase signaling (10) Spry2 can function as a regulator of mitogen-activated protein kinase signaling, which plays a crucial role in the regulation of cancer cell invasion (11,12). The protein level of Spry2 has previously been reported to be significantly decreased in invasive glioma tissues, suggesting that Spry2 may participate...