miR-25 promotes glioblastoma cell proliferation and invasion by directly targeting NEFL

Abstract

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.

Upregulation of microRNA-25-3p inhibits proliferation, migration and invasion of osteosarcoma cells in vitro by directly targeting SOX4

“…Li et al (25) reported that miR-25-3p expression is enhanced in gastric cancer tumor tissue, and its increased expression is correlated with tumor node metastasis stage and lymph node metastasis. The upregulation of miR-25-3p has also been observed in hepatocellular carcinoma (26), glioblastoma (27), glioma (28), cervical cancer (29) and cholangiocarcinoma (30).…”

“…In lung cancer cells, miR-25-3p overexpression was demonstrated to promote cellular proliferation and motility, and decrease apoptosis in vitro, and to enhance tumor growth in vivo; however, contradictory studies have reported that miR-25-3p overexpression enhances the sensitivity of lung cancer cells to cisplatin and promotes cell cycle arrest in the G 1 phase in vitro, by modulating FBXW7, regulator of G protein signaling 3, modulator of apoptosis 1, cell division control protein 42 homolog and cyclin E2 (38)(39)(40)(41). Peng et al (27) revealed that miR-25-3p overexpression potentiates the proliferation and invasion of glioblastoma cells in vitro, through the regulation of neurofilament light. These findings suggest that there remains controversy around the role of miR-25-3p in human cancer, and further studies are required on the matter.…”

NEFM (Neurofilament Medium) Polypeptide, a Marker for Zona Glomerulosa Cells in Human Adrenal, Inhibits D1R (Dopamine D1 Receptor)–Mediated Secretion of Aldosterone

“…29 In brain and extraneuronal cancer NEFM, NEFL and NEFH play a role as onco-suppressors because their epigenetic silencing affects cell proliferation and correlates with aggressiveness and prognosis. [30][31][32][33] Similar to other upregulated genes in human ZG, we found that NEFM suppresses aldosterone secretion and cell proliferation. In addition, it reduced dopamine stimulation of D1R responses.…”

miR‑25‑3p promotes glioma cell proliferation and migration by targeting FBXW7 and DKK3

“…Furthermore, exosome-derived miR-25 stimulates the malignant progression of liposarcoma (13). Zhang et al (14) reported that miR-25 promoted glioma cell proliferation by targeting cyclin dependent kinase inhibitor 1C, while Peng et al (15) demonstrated that miR-25 promoted glioblastoma cell proliferation and invasion by directly targeting neurofilament light. However, the clinical significance of miR-25 expression in glioma as well as the underlying molecular mechanism of miR-25 in glioma cell proliferation and migration remains unknown.…”