miR-25 promotes glioblastoma cell proliferation and invasion by directly targeting NEFL
- 421 Downloads
Glioblastoma multiforme (GBM) is the most malignant and common brain tumor; it is aggressive growth pattern means that GBM patients face a poor prognosis even when receiving the best available treatment modalities. In recent years, an increasing number of reports suggest that the discovery of microRNAs (miRNAs) might provide a novel therapeutic target for human cancers, including GBM. One miRNA in particular, microRNA-25 (miR-25), is overexpressed in several cancers, wherein accumulating evidence indicates that it functions as an oncogene. However, the function of miR-25 in GBM has not been totally elucidated. In this study, we demonstrated that miR-25 was significantly up-regulated in astrocytoma tissues and glioblastoma cell lines. In vitro studies further demonstrated that overexpressed miR-25 was able to promote, while its antisense oligos inhibited cell proliferation and invasion in U251 cells. Moreover, we identified neurofilament light polypeptide (NEFL) as a novel target molecule of miR-25. Also of note was the fact that NEFL was down-regulated with increased levels of miR-25 expression in human astrocytoma clinical specimens. In addition, via the mTOR signaling pathway, NEFL-siRNA could significantly attenuate the inhibitory effects of knockdown miR-25 on the proliferation and invasion of U251 cells. Overall, our results showed an important role for miR-25 in regulating NEFL expression in GBM, and suggest that miR-25 could be a potential target for GBM treatment.
KeywordsmiR-25 NEFL Glioblastoma Cell proliferation and invasion
The authors thank Dr. Zeyou Wang for his precious suggestions and generous help in carrying out this study.
Compliance with Ethical Standards
Conflict of interest
The authors declare no competing financial interests.
- 13.Wang Z, Yang J, Xu G, Wang W, Liu C, Yang H, Yu Z, Lei Q, Xiao L, Xiong J, Zeng L, Xiang J, Ma J, Li G, Wu M (2015) Targeting miR-381-NEFL axis sensitizes glioblastoma cells to temozolomide by regulating stemness factors and multidrug resistance factors. Oncotarget 6:3147–3164PubMedCentralCrossRefPubMedGoogle Scholar
- 17.Li BS, Zuo QF, Zhao YL, Xiao B, Zhuang Y, Mao XH, Wu C, Yang SM, Zeng H, Zou QM, Guo G (2014) MicroRNA-25 promotes gastric cancer migration, invasion and proliferation by directly targeting transducer of ERBB2, 1 and correlates with poor survival. Oncogene 34(20):2556–2565. doi: 10.1038/onc.2014.214 CrossRefPubMedGoogle Scholar
- 22.Xu X, Chen Z, Zhao X, Wang J, Ding D, Wang Z, Tan F, Tan X, Zhou F, Sun J, Sun N, Gao Y, Shao K, Li N, Qiu B, He J (2012) MicroRNA-25 promotes cell migration and invasion in esophageal squamous cell carcinoma. Biochem Biophys Res Commun 421:640–645. doi: 10.1016/j.bbrc.2012.03.048 CrossRefPubMedGoogle Scholar
- 23.Razumilava N, Bronk SF, Smoot RL, Fingas CD, Werneburg NW, Roberts LR, Mott JL (2012) miR-25 targets TNF-related apoptosis inducing ligand (TRAIL) death receptor-4 and promotes apoptosis resistance in cholangiocarcinoma. Hepatology 55:465–475. doi: 10.1002/hep.24698 PubMedCentralCrossRefPubMedGoogle Scholar
- 24.Poliseno L, Salmena L, Riccardi L, Fornari A, Song MS, Hobbs RM, Sportoletti P, Varmeh S, Egia A, Fedele G, Rameh L, Loda M, Pandolfi PP (2010) Identification of the miR-106b ~25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation. Sci Signal 3:a29. doi: 10.1126/scisignal.2000594 CrossRefGoogle Scholar
- 26.Haddad LA, Smith N, Bowser M, Niida Y, Murthy V, Gonzalez-Agosti C, Ramesh V (2002) The TSC1 tumor suppressor hamartin interacts with neurofilament-L and possibly functions as a novel integrator of the neuronal cytoskeleton. J Biol Chem 277:44180–44186. doi: 10.1074/jbc.M207211200 CrossRefPubMedGoogle Scholar