Abstract
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.
Highlights
Glioma is one of the most malignant tumors and accounts for more than 80% of all primary malignant tumors of the central nervous system [1]
MiR-325-3p levels were lower in the glioma cell lines when compared to the astrocytes (Fig. 2B)
These results suggested that miR-325-3p is a promising prognostic biomarker for glioma and may contribute to malignant progression
Summary
Glioma is one of the most malignant tumors and accounts for more than 80% of all primary malignant tumors of the central nervous system [1]. Surgery, chemotherapy, and radiotherapy are the main strategies for glioma treatment [3]. This disease is virtually incurable, and its five-year survival rate remains unsatisfactorily low [4]. MiRNAs are endogenous, non-coding RNAs that regulate multiple physiological and pathological processes at the posttranscriptional level [6,7,8] and mounting evidence suggests the involvement of miRNAs in multiple cancers, including glioma. MiR-325-3p showed low expression levels in colorectal cancer (CRC), representing a key regulator of bone metastasis [9]. In gastric cancer (GC), the miR-325-3p was decreased, and its low expression level was associated with metastasis [10]. The exact functions of miR-325-3p in glioma have yet to be determined, and these data suggest that miR-325-3p could be a potential therapeutic target for malignant glioma (Fig. 1)
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