MiR-۱۰۳ alleviates autophagy and apoptosis by regulating SOX۲ in LPS-injured PC۱۲ cells and SCI rats

Objective(s): Recent studies revealed that microRNAs (miRNAs) may play crucial roles in the responses and pathologic processes of spinal cord injury (SCI). This study aimed to investigate the effect and the molecular basis of miR-۱۰۳ on LPS-induced injuries in PC۱۲ cells in vitro and SCI rats in vivo. Materials and Methods: PC۱۲ cells were exposed to LPS to induce cell injuries to mimic the in vitro model of SCI. The expression of miR-۱۰۳ and SOX۲ in PC۱۲ cells were altered by transient transfections. Cell viability and apoptotic cell rate were measured by CCK-۸ assay and flow cytometry assay. Furthermore, Western blot analysis was performed to detect the expression levels of apoptosis- and autophagy- related proteins, MAPK/ERK pathway- and JAK/STAT pathway-related proteins. In addition, we also assessed the effect of miR-۱۰۳ agomir on SCI rats. Results: LPS exposure induced cell injuries in PC۱۲ cells. miR-۱۰۳ overexpression significantly increased cell viability, reduced cell apoptosis and autophagy, and opposite results were observed in miR-۱۰۳ inhibition. miR-۱۰۳ attenuated LPS-induced injuries by indirect upregulation of SOX۲. SOX۲ overexpression protected PC۱۲ cells against LPS-induced injuries, while SOX۲ inhibition expedited LPS-induced cell injuries. Furthermore, miR-۱۰۳ overexpression inhibited MAPK/ERK pathway and JAK/STAT pathway through upregulation of SOX۲. We also found that miR-۱۰۳ agomir inhibited cell apoptosis and autophagy in SCI rats. Conclusion: This study demonstrates that miR-۱۰۳ may represent a protective effect against cell apoptosis and autophagy in LPS-injured PC۱۲ cells and SCI rats by upregulation of SOX۲ expression.

Keywords:

Apoptosis , Autophagy , MAPK/ERK and JAK/STAT pathway , miR-۱۰۳ , SOX۲ , Spinal cord injury