التفاصيل البيبلوغرافية
| العنوان: |
Lysine tRNA fragments and miR-194-5p co-regulate hepatic steatosis via β-Klotho and perilipin 2 |
| المؤلفون: |
Yonat Tzur, Katarzyna Winek, Nimrod Madrer, Serafima Dubnov, Estelle R. Bennett, David S. Greenberg, Geula Hanin, Asaad Gammal, Joseph Tam, Isaiah T. Arkin, Iddo Paldor, Hermona Soreq |
| المصدر: |
Molecular Metabolism, Vol 79, Iss , Pp 101856- (2024) |
| بيانات النشر: |
Elsevier, 2024. |
| سنة النشر: |
2024 |
| المجموعة: |
LCC:Internal medicine |
| مصطلحات موضوعية: |
KLB, LysTTT-5′tRFs, microRNAs, miR-194-5p, NAFLD, PLIN2, Internal medicine, RC31-1245 |
| الوصف: |
Objective: Non-alcoholic fatty liver disease (NAFLD) involves hepatic accumulation of intracellular lipid droplets via incompletely understood processes. Here, we report distinct and cooperative NAFLD roles of LysTTT-5′tRF transfer RNA fragments and microRNA miR-194-5p. Methods: Combined use of diet induced obese mice with human-derived oleic acid-exposed Hep G2 cells revealed new NAFLD roles of LysTTT-5′tRF and miR-194-5p. Results: Unlike lean animals, dietary-induced NAFLD mice showed concurrent hepatic decrease of both LysTTT-5′tRF and miR-194-5p levels, which were restored following miR-132 antisense oligonucleotide treatment which suppresses hepatic steatosis. Moreover, exposing human-derived Hep G2 cells to oleic acid for 7 days co-suppressed miR-194-5p and LysTTT-5′tRF levels while increasing lipid accumulation. Inversely, transfecting fattened cells with a synthetic LysTTT-5′tRF mimic elevated mRNA levels of the metabolic regulator β-Klotho while decreasing triglyceride amounts by 30% within 24 h. In contradistinction, antisense suppression of miR-194-5p induced accumulation of its novel target, the NAFLD-implicated lipid droplet-coating PLIN2 protein. Further, two out of 15 steatosis-alleviating screened drug-repurposing compounds, Danazol and Latanoprost, elevated miR-194-5p or LysTTT-5′tRF levels. Conclusion: Our findings highlight the different yet complementary roles of miR-194-5p and LysTTT-5′tRF and offer new insights into the complex roles of small non-coding RNAs and the multiple pathways involved in NAFLD pathogenesis. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2212-8778 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2212877823001904; https://doaj.org/toc/2212-8778 |
| DOI: |
10.1016/j.molmet.2023.101856 |
| URL الوصول: |
https://doaj.org/article/10e908bb94994ad399d128f2b5fc3d68 |
| رقم الانضمام: |
edsdoj.10e908bb94994ad399d128f2b5fc3d68 |
| قاعدة البيانات: |
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