English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Dyslipidemia exhibits a high incidence after liver transplantation, in which tacrolimus, a widely used immunosuppressant, plays a fundamental role. MicroRNAs and related circRNAs represent a class of noncoding RNAs that have been recognized as important regulators of genes associated with lipid metabolism. However, their transcriptional activities and functional mechanisms in tacrolimus-related dyslipidemia remain unclear. In this study, we observed that tacrolimus could induce triglyceride accumulation in hepatocytes by stimulating sterol response element-binding proteins (SREBPs) and miR-33a. Our in silico and experimental analyses identified miR-33a as a direct target of circFASN. Tacrolimus could downregulate circFASN and result in elevated miR-33a in vivo and in vitro. Overexpression of circFASN or silencing of miR-33a decreased the promoting effects of tacrolimus on triglyceride accumulation. Clinically, the incidence of dyslipidemia in liver transplant recipients with elevated serum miR-33a after liver transplantation was higher than that in patients without elevated serum miR-33a (46.3% vs. 18.8%  p  = 0.012,  n  = 73). Our results showed that the circFASN/miR-33a regulatory system plays a distinct role in tacrolimus-induced disruption of lipid homeostasis. MiR-33a is likely a risk factor for tacrolimus-related dyslipidemia, providing a potential therapeutic target to combat tacrolimus-induced dyslipidemia after liver transplantation.

The circFASN/miR-33a pathway participates in tacrolimus-induced dysregulation of hepatic triglyceride homeostasis