miR-144-3p serves as a tumor suppressor by targeting FZD7 and predicts the prognosis of human glioblastoma

OBJECTIVE: Previous research indicated that miR-144-3p was associated with the regulation of the carcinogenic processes, but the role of miR-144-3p in glioblastoma (GBM) remains unclear. In this study, we aimed to analyze the role of miR-144-3p in GBM.

PATIENTS AND METHODS: The expression of miR-144-3p was measured in GBM tissues and adjacent non-malignant tissues using qRT-PCR. The correlation of miR-144-3p with clinicopathological features and prognosis was also analyzed. Cell proliferation, invasion, and migration assay were applied to assess the function of miR-144-3p in vitro. Bioinformatics prediction and luciferase assays were employed to identify the predicted microRNA (miRNA) which regulates Frizzled-7 (FZD7). The levels of FZD7 and FZD7 mRNA were determined by Western blot and RT-PCR.

RESULTS: The results showed that the miR-144-3p expression was significantly downregulated in tumor tissues and GBM cell lines compared with that in normal brain tissues and the normal human astrocytes. The levels of miR-144-3p were negatively correlated with the status of WHO grade and recurrence. Furthermore, patients with low serum levels of miR-144-3p had a significantly shorter median overall survival rate. Multivariate Cox regression analysis confirmed that low level of miR-144-3p expression predicted poor prognosis independently. Further function assays showed that miR-144-3p inhibited proliferation invasion and migration of GBM cells. Finally, miR-144-3p was demonstrated to bind to the wild-type 3' untranslated region of FZD7 but not with its mutant.

CONCLUSIONS: The results of the present study indicate that miR-144-3p suppresses tumor metastasis by targeting FZD7. This work also provides strong evidence that miR-144-3p is an independent prognostic factor for patients with GBM.

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