The aberrant expression of microRNA-375 (miR-375) has been proven to be associated with carcinogenesis. However, the role of miR-375 in glioblastoma (GBM) remains unknown. The aim of this study was to investigate miR-375 biological functions and its molecular mechanisms in GBM cells. In this study, real-time PCR results showed that the level of miR-375 expression in GBM tissues and GBM cell lines (U87 and U251) was decreased. Using MTT assay, trans-well migration and invasion assay, we demonstrated that miR-375 overexpression significantly suppress cell proliferation, cell migration and cell invasion capacity in U87 and U251 cells. However, downregulation of miR-375 had reverse effects on cell proliferation, migration and invasion. In association analysis, dual luciferase assay, RT-PCR and western blot analysis results confirmed that miR-375 could target the 3'UTR of Wnt5a mRNA and regulate its protein expression. Further studies also showed that Wnt5a overexpression significantly reversed miR-375-mediated proliferation, migration and invasion in U87 and U251 cells. Therefore, we concluded that miR-375 inhibits proliferation and invasion of GBM by regulating Wnt5a and therefore might be a possible therapeutic agent for GBM.

Mesenchymal stem cells (MSCs) have been considered a potential method for the regeneration of tooth and maxillofacial bone defects based on the multidirectional differentiation characteristics of MSCs. miRNAs have been found to play a key role in the differentiation of MSCs. However, its effectiveness still needs to be improved, and its internal mechanism is still unclear. In the present study, our data discovered that the knockdown of miR-196b-5p promoted alkaline phosphatase (ALP) activity assay, mineralization in vitro, and expressions of osteo/odontogenic differentiation markers DSPP and OCN and enhanced in vivo osteo/odontogenic differentiation of stem cells of the apical papilla (SCAPs). Mechanistically, the results indicated that METTL3-dependent N6-methyladenosine (m6A) methylation inhibited miR-196b-5p maturation by the microprocessor protein DGCR8. Moreover, miR-196b-5p indirectly negatively regulates METTL3 in SCAPs. Then, METTL3 was found to strengthen the ALP activity assay, mineralization, and expressions of osteo/dentinogenic differentiation markers. Taken together, our findings highlight the critical roles of the METTL3-miR-196b-5p signaling axis in an m6A-dependent manner in osteo/odontogenic differentiation of SCAPs, identifying some potential targets for tooth and maxillofacial bone defects.

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