Resveratrol promotes mitophagy via the MALAT1/miR-143-3p/RRM2 axis and suppresses cancer progression in hepatocellular carcinoma  

作　　者：Chun-yan Feng Cheng-song Cai Xiao-qian Shi Zhi-juan Zhang Dan Su Yun-qing Qiu 

机构地区：[1]National Key Laboratory of Diagnosis and Treatment of Severe Infectious Disease,National Clinical Research Center for Infectious Diseases,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation,the First Affiliated Hospital,College of Medicine,Zhejiang University,Hangzhou 310000,Zhejiang Province,China [2]Department of Clinical Medicine,Hangzhou Medical College,Hangzhou 310053,Zhejiang Province,China [3]Department of Clinical Laboratory,the Affiliated Hospital of Hangzhou Normal University,Hangzhou 310015,Zhejiang Province,China

出　　处：《Journal of Integrative Medicine》2025年第1期79-92,共14页结合医学学报(英文版)

基　　金：supported by the Zhejiang Provincial Science and Technology Department Key Research and Development Plan(No.2020C03046).

摘　　要：Objective Resveratrol(Res)is a promising anticancer drug against hepatocellular carcinoma(HCC),but whether its anti-HCC effects implicate mitophagy remains unclear.Therefore,we aimed to explore the specific role of Res in mitophagy and the related mechanisms during the treatment of HCC.Methods HepG2 cells and tumor-grafted nude mice were used to investigate the effects of low-,middle-and high-dose of Res on HCC progression and mitophagy in vitro and in vivo,respectively.A series of approaches including cell counting kit-8,flow cytometry,wound healing and transwell assays were used to evaluate tumor cell functions.Transmission electron microscopy,immunofluorescence and Western blotting analysis were used to assess mitophagy.Mitochondrial oxygen consumption rate,reactive oxygen species and membrane potential were used to reflect mitochondrial function.After disrupting the expression of metastasis-associated lung adenocarcinoma transcript 1(MALAT1),miR-143-3p,and ribonucleoside reductase M2(RRM2),the effects of the MALAT1/miR-143-3p/RRM2 axis on cell function and mitophagy under Res treatment were explored in vitro.Additionally,dual-luciferase reporter and chromatin immunoprecipitation were used to confirm interactions between target genes.Results Res significantly inhibited the proliferation and promoted apoptosis of HCC cells in vitro,while significantly suppressing tumor growth in a dose-dependent manner and inducing mitophagy and mitochondrial dysfunction in vivo.Interestingly,MALAT1 was highly expressed in HCC cells and its knockdown upregulated miR-143-3p expression in HCC cells,which subsequently inhibited RRM2 expression.Furthermore,in nude mice grafted with HCC tumors and treated with Res,the expression of MALAT1,miR-143-3p and RRM2 were altered significantly.In vitro data further supported the targeted binding relationships between MALAT1 and miR-143-3p and between miR-143-3p and RRM2.Therefore,a series of cell-based experiments were carried out to study the mechanism of the MALAT1/miR-143-3p/RRM2 axis inv

关 键 词：Hepatocellular carcinoma RESVERATROL MITOPHAGY MALAT1 miR-143-3p 

分 类 号：R285[医药卫生—中药学]