Downregulation of Promotes Autophagy and Cell Survival by Targeting TSC1/mTOR Signaling in NSC-34 Cells.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of upper and lower motor neurons. MicroRNAs (miRNAs) are reported to be closely related to the development of ALS. However, the precise functions of miRNAs in the pathogenesis of ALS remain largely unknown. In previous studies, we determined that was significantly downregulated in patients with sporadic ALS (sALS). Here, we observed that was downregulated in the SOD1 mouse model of ALS and promoted cell death in NSC-34 cells. We further found that directly targeted tuberous sclerosis 1 (TSC1) to regulate mechanistic target of rapamycin complex 1 (mTORC1) activity. Downregulation of led to TSC1 increase accompanied with mTORC1 inactivation, and . Moreover, downregulation of promoted protective autophagy and cell survival in NSC-34 cells. In contrast, upregulation of activated mTORC1 signaling, leading to inhibition of autophagy and promotion of cell death. Taken together, our study suggests that downregulation of is required for cell survival by targeting TSC1/mTOR signaling in NSC-34 cells and provides a novel target for improving the clinical therapy of ALS.