miR‑96 inhibits EMT by targeting AEG‑1 in glioblastoma cancer cells

Abstract

The induction of epithelial to mesenchymal transition (EMT) is important for carcinogenesis and cancer progression. Previous studies have estimated that microRNA (miRNA/miR) expression is associated with EMT via the regulation of the expression of target genes. miR-96 has been reported to exhibit a correlation with the EMT process. However, the functional role of miR-96 and its mechanism in glioblastoma multiforme (GBM) remains to be completely elucidated. The objective of the present study was to investigate the functional role and mechanism of miR-96 in the migration and invasion, in addition to proliferation, apoptosis and cell cycle distribution, of GBM. In the present study, the results suggested that the introduction of miR-96 significantly inhibited the migration and invasion, in addition to proliferation and cell cycle progression, of GBM cells and promoted their apoptosis in vitro, leading to the hypothesis that miR-96 may be a potential tumor suppressor. It was subsequently confirmed that astrocyte elevated gene-1 (AEG-1) was a direct target gene of miR-96, using a luciferase assay and reverse transcription-quantitative polymerase chain reaction analysis, in addition to western blotting. miR-96 was observed to downregulate the expression of AEG-1 at the mRNA and protein levels. Notably, AEG-1 may suppress EMT by increasing the expression levels of E-cadherin, an epithelial marker, and decreasing the expression levels of vimentin, a mesenchymal marker. Therefore, it was concluded that miR-96 may impede the EMT process by downregulating AEG-1 in GBM. Additionally, it was observed that inhibition of AEG-1 led to a similar effect compared with overexpression of miR-96 in GBM. In conclusion, the results of the present study demonstrated that miR-96 may act as a tumor suppressor by regulating EMT via targeting of AEG-1, suggesting that miR-96 may be a potential biomarker and anticancer therapeutic target for GBM in the future.

Identification and functional analysis of microRNAs in rats following focal cerebral ischemia injury

“…Chang and Lai (17) demonstrated that miR-96 may be used as a biomarker of ischemia-reperfusion injury in skin tissues. A recent study observed that miR-96 may represent a potential anticancer therapeutic target to treat glioblastoma (35). miR-96 was previously observed to serve as an oncosuppressor gene by targeting NUAK family kinase 1 in pancreatic cancer (36).…”

Mesenchymal Transformation: The Rosetta Stone of Glioblastoma Pathogenesis and Therapy Resistance

“…Similarly, miR-140, miR-101-3p, miR-577, miR-96, and miR211 suppressed GBM mesenchymal properties by targeting cathepsin B, TRIM44, Rab25, AEG-1, and HMGA2, respectively. [77][78][79][80][81] On the other hand, aberrant expression of miR-10b is associated with grade IV gliomas as well as PMT. [82] Agomir (a miRNA mimic) of miR-10b injection enhances tumor growth in vivo, while miR-10b mimics induces a significant morphological change of GBM cells from pebble shape to the long fusiform shape, a feature of PMT.…”

<p>MicroRNA 885-5p Inhibits Hepatocellular Carcinoma Metastasis by Repressing AEG1</p>

“…Overexpression of AEG1 has been documented to be involved in many tumors' biological processes, including tumor proliferation, metastasis, EMT. [12][13][14][15] To evaluate the possibility that AEG1 is important for HCC, we examined AEG1 expression in corresponding noncancerous tissues and HCC using Gene Expression Profiling Interactive Analysis (GEPIA) website based on TCGA database. 16 Notably, AEG1 expression in HCC samples was significantly higher compared to normal samples ( Figure 3A).…”