Diosbulbin B induced G2 /M cell cycle arrest in hepatocytes by miRNA-186-3p and miRNA-378a-5p-mediated the decreased expression of CDK1

Toxicology and Applied Pharmacology
Rui YangLili Ji

Abstract

Diosbulbin B (DB) is the main hepatotoxic compound in Airpotato yam, which is traditionally used for treating thyroid disease and cancer in China, and its hepatotoxic mechanism still remains unclear. This study aims to investigate its hepatotoxic mechanism by focusing on regulating microRNA (miRNA). DB induced hepatotoxicity both in vivo and in vitro. Results of miRNA chip analysis showed that the expression of eleven miRNAs was up-regulated and twelve miRNAs was down-regulated in livers from DB-treated mice. The altered expression of seven miRNAs was further validated by using real-time polymerase chain reaction (RT-PCR) assay. DB induced G2/M arrest in L-02/cytochrome P450 3A4 (CYP3A4) cells in both concentration- and time-dependent manner. A total of eleven predicted target genes was related with cell cycle regulation of those above seven miRNAs, among which the mRNA and protein expression of cyclin-dependent kinase 1 (CDK1) decreased both in vivo and in vitro. Both miR-378a-5p and miR-186-3p have binding sites in the 3'-untranslated region (UTR) of CDK1. With the use of CDK1 3'-UTR luciferase reporter assay, miR-378a-5p and miR-186-3p was found to down-regulate the luciferase activity. The mimics of miR-378a-5p or miR-186-3...Continue Reading

Citations

May 11, 2019·Journal of Cellular Biochemistry·Jingyong TanJing Li
Apr 30, 2020·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Weiwei GaoRuihua Lin
Sep 23, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Chunfeng LiYingwei Xue
Jul 14, 2021·World Journal of Surgical Oncology·Xiurong LuZhilin Zhang

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