NEAT1/hsa-miR-372–3p axis participates in rapamycin-induced lipid metabolic disorder

• Published in: Free radical biology & medicine 2021-05, Vol.167, p.1-11
• Main Authors: Fan, Guanghan, Zhang, Chenzhi, Wei, Xuyong, Wei, Rongli, Qi, Zhetuo, Chen, Kangchen, Cai, Xuechun, Xu, Li, Tang, Linsong, Zhou, Junbin, Zhang, Zhensheng, Lin, Zuyuan, Xie, Haiyang, Zheng, Shusen, Fan, Weimin, Xu, Xiao
• Format: Article
• Language: English
• Subjects: Dyslipidemia; Liver transplantation; microRNA; Rapamycin; Triglyceride metabolism
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2021.02.033

Rapamycin is a crucial immunosuppressive regimen for patients that have undergone liver transplantation (LT). However, one of the major side effects of rapamycin include metabolic disorders such as dyslipidemia, and the mechanism remains unknown. This study aims to explore the biomolecules that are responsible for rapamycin-induced dyslipidemia and the control strategies that can reverse the lipid metabolism disorder. In this study, data collected from LT patients, cell and mouse models treated with rapamycin were analyzed. Results showed an increase of triglycerides (TGs) induced by rapamycin. MicroRNAs (miRNAs) play important roles in many vital biological processes including TG metabolism. hsa-miR-372–3p was filtered using RNA sequencing and identified as a key regulator in rapamycin-induced TGs accumulation. Using bioinformatics and experimental analyses, target genes of hsa-miR-372–3p were predicted. These genes were alkylglycerone phosphate synthase (AGPS) and apolipoprotein C4 (APOC4), which are reported to be involved in TG metabolism. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was also identified as an upstream regulatory factor of hsa-miR-372–3p. From the results of this study, NEAT1/hsa-miR-372–3p/AGPS/APOC4 axis plays a vital role in rapamycin-disruption of lipid homeostasis. Therefore, targeting this axis is a potential therapeutic target combating rapamycin-induced dyslipidemia after LT. [Display omitted] •Rapamycin can induce lipid metabolic disorder after liver transplantation.•Expression of hsa-miR-372–3p was decreased significantly after using rapamycin.•NEAT1/hsa-miR-372–3p/AGPS/APOC4 axis participates in rapamycin-related lipid metabolic disorder.