Overexpressed miRNA-nov-1 promotes manganese-induced apoptosis in N27 cells by regulating Dhrs3 to activate mTOR signaling pathway

Environmental and occupational chronic manganese exposure can cause neurotoxicity and apoptosis. Moreover, microRNAs (miRNAs) are extensively involved in the process of neuronal apoptosis. Therefore, it is crucial to study the mechanism of miRNA in manganese-induced neuronal apoptosis and to find potential targets. In the present study, we found that the expression of miRNA-nov-1 was increased after N27 cells were exposed to MnCl2. Then, seven different cell groups were constructed by lentiviral infection of cells, and the overexpression of miRNA-nov-1 promoted the apoptosis process of N27 cells. Further studies showed a negative regulatory relationship between miRNA-nov-1 and dehydrogenase/reductase 3 (Dhrs3). The up-regulation of miRNA-nov-1 reduced the protein level of Dhrs3 in N27 cells exposed to manganese, increased the expression of a caspase-3 protein, activated the rapamycin (mTOR) signaling pathway, and increased cell apoptosis. Furthermore, we found that the expression of the Caspase-3 protein was decreased after the low expression of miRNA-nov-1, the mTOR signaling pathway was inhibited, and reduced cell apoptosis. However, these effects were reversed by the knockdown of Dhrs3. Taken together, these results suggested that overexpression of miRNA-nov-1 can promote manganese-induced apoptosis in N27 cells by activating the mTOR signaling pathway and negatively regulating Dhrs3.

Automated summary

In this study, it was found that the expression of miRNA-nov-1 increased in N27 cells exposed to manganese and overexpression of miRNA-nov-1 promoted apoptosis in these cells. Further investigations revealed a negative regulatory relationship between miRNA-nov-1 and Dhrs3. Overexpression of miRNA-nov-1 reduced the protein level of Dhrs3, increased caspase-3 protein expression, activated the mTOR signaling pathway, and enhanced cell apoptosis in manganese-exposed N27 cells. Conversely, low expression of miRNA-nov-1 decreased Caspase-3 protein expression, suppressed the mTOR signaling pathway, and reduced cell apoptosis. However, these effects were reversed by knockdown of Dhrs3.