MicroRNA-103 suppresses glioma cell proliferation and invasion by targeting the brain-derived neurotrophic factor

Abstract

Glioma is the most common and aggressive of malignant brain tumours. MicroRNAs (miRNAs/miRs) are involved in tumour development of various human cancers, including glioma. Therefore, miRNAs may have potential tumour diagnostic, prognostic and therapeutic values in human glioma. miR‑103 is abnormally expressed in various human cancer types. However, the detailed expression pattern, biological functions and underlying molecular mechanism of miR‑103 in glioma remain unclear. Therefore, the present study aimed to investigate the expression, biological roles and underlying mechanisms of miR‑103 in glioma. Results of the present study demonstrated that miR‑103 was significantly down‑regulated in glioma tissues and cell lines. Functional experiments demonstrated that miR‑103 overexpression inhibited the proliferation and invasion of glioma cells in vitro. Additionally, brain‑derived neurotrophic factor (BDNF) was identified as a direct functional target of miR‑103 in glioma. Furthermore, mRNA and protein expression levels of BDNF were highly upregulated in glioma tissues compared with normal brain tissues. Spearman's correlation analysis indicated a negative association between miR‑103 and BDNF mRNA expression levels in glioma tissues. Furthermore, rescue experiments demonstrated that BDNF up‑regulation reversed the suppressive effects of miR‑103 on glioma cell proliferation and invasion. Therefore, the authors of the present study hypothesized that the interaction between miR‑103 and BDNF serves a role in glioma progression and, in the future, may serve as a therapeutic target for glioma treatment.

P2X4R silence suppresses glioma cell growth through BDNF/TrkB/ATF4 signaling pathway

“…ATF4, activating transcription factor 4; BDNF, brain-derived neurotrophic factor; ELISA, enzyme-linked immunosorbent assay; P2X4R, purinergic receptor P2X 4; siRNA, small interfering RNA; TrkB, Trk receptor tyrosine kinases BDNF expression at mRNA and protein levels were markedly increased in glioma tissues; moreover, decreased BDNF expression by miR-103 inhibits glioma cell proliferation and invasion. 29 Consistent with these reports, our study confirmed that P2X4R silence blocked BDNF/TrkB expression and plays inhibitory role in glioma cell growth. We also confirmed that BDNF overexpression increased TrkB expression compared with P2X4R silence group; however, TrkB overexpression has no obvious effects on BDNF expression.…”

“…28,29 There has ample evidence indicated that TrkB is a receptor of BDNF and play roles in the action of BDNF. 29 Consistent with these reports, our study confirmed that P2X4R silence blocked BDNF/TrkB expression and plays inhibitory role in glioma cell growth. A, ATF4 expression in U87 and T98 cells were determined by Western blot analysis.…”

The inhibition of BDNF/TrkB/PI3K/Akt signal mediated by AG1601 promotes apoptosis in malignant glioma

“…According to the role of BDNF/TrkB/PI3K/Akt signal, we focused on this signal as the underlying mechanism of AG1601 anticancer effects on glioma. Some studies also showed that the recombinant mature BDNF protein, as an activator of BDNF/TrkB signal, could promote the proliferation of glioma cells . Our study also showed that BDNF reversed the inhibitory effects of AG1601 on proliferation of C6 cells (Figure A).…”

“…Some studies also showed that the recombinant mature BDNF protein, as an activator of BDNF/TrkB signal, could promote the proliferation of glioma cells. 8,26,27 Our study also showed that BDNF reversed the inhibitory effects of AG1601 on proliferation of C6 cells ( Figure 3A). BDNF also resisted C6 cell apoptosis induced by AG1601.…”

“…In the previous study, it has been reported that the series of AG drugs, including AG1031 and AG1503, effectively suppressed the proliferation and induced the apoptosis of C6 glioma cells. 26 AG1601 has been optimized on the basis of other AG-series drugs. In our study, AG1601 also has good effects on the antiproliferation and pro-apoptosis of C6 glioma cells.…”