MiR-185-induced autophagy is associated with triglyceride accumulation

L. Zhou, A. Ma, Y. Wang, S. Liu, J. Cheng

Article ID: 5021
Vol 36, Issue 2, 2022
DOI: https://doi.org/10.23812/21-467-A
Received: 21 November 2021; Accepted: 21 November 2021; Available online: 9 May 2022; Issue release: 9 May 2022

Abstract

Studies have demonstrated that miRNA-185 may be a promising therapeutic target for NAFLD.However, the underlying mechanisms have not been fully clarified. Autophagy, an evolutionarilyconserved catabolic process, maintains cellular homeostasis under stressful conditions, and it is closelyassociated with metabolic disorders. We previously reported that miR-185 could regulate autophagyfor the first time via decreasing target genes (RHEB and RICTOR). The present study found thatmiR-185-induced autophagy is responsible for triglyceride (TG) accumulation. Firstly, we confirmedthe regulatory relationship between miR-185 and lipid metabolism. Then, we found that nutrientdeprivation upregulated the miR-185 level, which is associated with a remarkable downregulation ofSREBP1C and FASN, as the main genes of TG synthesis, and also RHEB and RICTOR. Furthermore,the downregulated expression levels of SREBP1C and FASN confirmed that nutrient deprivation coulddecrease lipid storage. The downregulated expression levels of RHEB and RICTOR and increasingLC3 II/LC3-I ratio suggested that autophagy plays a role in lipid accumulation. The results highlightedan important potential role for miR-185-induced autophagy in TG accumulation. Additionally, it wasfound that the autophagosome level was upregulated with si-RHEB or si-RICTOR, which was consistentwith the conversion of LC3-I to LC3-II. The downregulated expression levels of SREBP1C and FASNconfirmed that the down-expression of RHEB or RICTOR could decrease TG accumulation. Therefore,the promotion of autophagy may be a promising therapeutic strategy for NAFLD, and miR-185 is apromising miRNA that can be developed and assessed for its significant clinical effects on NAFLD.


Keywords

triglyceride accumulation;microRNA-185;RHEB;RICTOR;autophagy


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