Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Query: UMLS:C0002736 (
amyotrophic lateral sclerosis
)
19,048
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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
miRNA-193b-3p
was significantly downregulated in patients with sporadic
ALS
(sALS). Here, we observed that
miRNA-193b-3p
was downregulated in the SOD1
G93A
mouse model of
ALS
and promoted cell death in NSC-34 cells. We further found that
miR-193b-3p
directly targeted
tuberous sclerosis 1
(
TSC1
) to regulate mechanistic target of rapamycin complex 1 (mTORC1) activity. Downregulation of
miR-193b-3p
led to
TSC1
increase accompanied with mTORC1 inactivation, and
vice versa
. Moreover, downregulation of
miR-193b-3p
promoted protective autophagy and cell survival in NSC-34 cells. In contrast, upregulation of
miR-193b-3p
activated mTORC1 signaling, leading to inhibition of autophagy and promotion of cell death. Taken together, our study suggests that downregulation of
miR-193b-3p
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
.
...
PMID:Downregulation of
MicroRNA-193b-3p
Promotes Autophagy and Cell Survival by Targeting TSC1/mTOR Signaling in NSC-34 Cells. 2861 87