Downregulation of long non-coding RNA AIRN promotes mitophagy in alcoholic fatty hepatocytes by promoting ubiquitination of mTOR
| Autor: | Li miao Lin, Sujian Shen, Jianzhang Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine F-Box-WD Repeat-Containing Protein 7 Physiology Down-Regulation Mitochondria Liver Cell Line 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Mitophagy Animals PI3K/AKT/mTOR pathway Gene knockdown biology Chemistry TOR Serine-Threonine Kinases Ubiquitination RNA Articles General Medicine Long non-coding RNA Cell biology Ubiquitin ligase Mice Inbred C57BL Disease Models Animal 030104 developmental biology Liver 030220 oncology & carcinogenesis Hepatocytes biology.protein RNA Long Noncoding Alcoholic fatty liver Fatty Liver Alcoholic Signal Transduction |
| Zdroj: | Physiol Res |
| ISSN: | 1802-9973 0862-8408 |
| DOI: | 10.33549/physiolres.934549 |
| Popis: | Long non-coding RNAs (lncRNAs) are crucial in chronic liver diseases, but the specific molecular mechanism of lncRNAs in alcoholic fatty liver (AFL) remains unclear. In this study, we investigated the in-depth regulatory mechanism of mTOR affected by AIRN non-protein coding RNA (lncRNA-AIRN) in the development of AFL. LncRNA-AIRN was highly expressed in the liver tissues of AFL C57BL/6 mice and oleic acid+alcohol (O+A) treated AML-12 cells by using quantitative real-time PCR. RNA pull-down and RNA immunoprecipitation experiments demonstrated that there was an interaction between lncRNA-AIRN and mTOR, and that interference with lncRNA-AIRN could promote the mTOR protein level. Results of cycloheximide-chase assay showed that the protein level of mTOR was decreased with the treatment time after the knockdown of lncRNA-AIRN. Furthermore, the knockdown of lncRNA-AIRN reduced mTOR protein level by promoting the E3 ubiquitin ligase FBXW7-mediated ubiquitination. The lncRNA-AIRN/mTOR axis was involved in the regulation of the mitophagy of O+A treated hepatocytes, which was confirmed by the cell transfection and the MTT assay. SPSS 16.0 was used for analyzing data. The difference between the two groups was analyzed by performing Student’s t-test, and ANOVA was used to analyze the difference when more than two groups. P values < 0.05 were considered to be significantly different. Our findings demonstrated that the knockdown of lncRNA-AIRN influenced mitophagy in AFL by promoting mTOR ubiquitination. |
| Databáze: | OpenAIRE |
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