Exosome-mediated transfer of circRNA563 promoting hepatocellular carcinoma by targeting the microRNA148a-3p/metal-regulatory transcription factor-1 pathway  

作　　者：Zhuo-Zhen Lyu Meng Li Ming-Yu Yang Mei-Hong Han Zhen Yang 

机构地区：[1]Department of Infectious Diseases,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250021,Shandong Province,China

出　　处：《World Journal of Gastroenterology》2023年第46期6060-6075,共16页世界胃肠病学杂志（英文版）

基　　金：the National Natural Science Foundation of China,No.81972606 and 82271774.

摘　　要：BACKGROUND Mesenchymal stem cells(MSCs)exert anti-oncogenic effects via exosomes containing non-coding RNA(ncRNA),which play important roles in tumor biology.Our preliminary study identified the interaction of the ncRNA hsa_-circ_0000563(circ563)and the circ563-associated miR-148a-3p in exosomes,as miR-148a-3p and its target metal-regulatory transcription factor-1(MTF-1)are implicated in hepatocellular carcinoma(HCC)progression.AIM To identify the clinical significance,functional implications,and mechanisms of circ563 in HCC.METHODS The expression levels of miR-148a-3p and MTF-1 in exosomes derived from MSC and HCC cells were compared,and their effects on HCC cells were assessed.Using a dual-luciferase reporter assay,miR-148a-3p was identified as an associated microRNA of circ563,whose role in HCC regulation was assessed in vitro and in vivo.RESULTS The silencing of circ563 blocked the HCC cell proliferation and invasion and induced apoptosis.Co-culturing of HCC cells with MSC-derived exosomes following circ563 overexpression promoted cell proliferation and metastasis and elicited changes in miR-148a-3p and MTF-1 expression.The tumor-promoting effects of circ563 were partially suppressed by miR-148a-3p overexpression or MTF-1 depletion.Xenograft experiments performed in nude mice confirmed that circ563-enriched exosomes facilitated tumor growth by upregulating the expression of MTF-1.In HCC tissues,circ563 expression was negatively correlated with miR-148a-3p expression but positively correlated with MTF-1 levels.CONCLUSION MSCs may exhibit anti-HCC activity through the exosomal circ563/miR-148a-3p/MTF-1 pathway,while exosomes can transmit circ563 to promote oncogenic behavior by competitively binding to miR-148a-3p to activate MTF-1.

关 键 词：EXOSOME Cell communication Noncoding RNA Metal-regulatory transcription factor-1 Mesenchymal stem cells 

分 类 号：R735.7[医药卫生—肿瘤]