MiR-325-3p functions as a suppressor miRNA and inhibits the proliferation and metastasis of glioma through targeting FOXM1

JOURNAL OF INTEGRATIVE NEUROSCIENCE(2021)

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摘要
Glioma is a malignant brain tumor exhibiting high levels of proliferation and metastasis, and these have been related to its poor prognosis and high mortality rate. MicroRNA (miRNA)-325-3p exhibits tissue-specific expression profiles and is aberrantly expressed in multiple types of malignant tumors. Our research focuses on determining the function and mechanism of action of miR-325-3p in glioma. The relative expression levels of miR-325-3p in glioma tumor tissues and cell lines were verified by qRT-PCR. The effect of 325-3p on glioma tumor cell behavior was assessed using CCK-8 assays, EDU staining, colony formation assays, flow cytometry, transwell invasion assays, and a xenograft model. In addition, we searched for miR-325-3p targets, and their potential mechanism of action was demonstrated using a reporter assay and rescue experiments. Results showed that the expression levels of miR-325-3p in glioma cancer tissues and tumor cell lines were significantly lower than that of normal paired adjacent tissue or normal cell lines. Functional experiments illustrated that tumor proliferation, migration and invasion were suppressed via upregulation of miR-325-3p. To assess whether FOXM1 is a target of miR-325-3p, we examined this hypothesis using a luciferase report assay and then found that miR-325-3p could modulate the expression of FOXM1. Furthermore, the functional role of miR-325-3p was also confirmed in a xenograft model using nude mice. Together, our data demonstrated that in glioma, miR-325-3p may inhibit cancer cell growth through the suppression of FOXM1 and could be a promising new target for treating this type of brain cancer.
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关键词
MiR-325-3p, FOXM1, Proliferation, Metastasis, Glioma, Neuro-oncology
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