Lyu ZZ, Li M, Yang MY, Han MH, Yang Z. Exosome-mediated transfer of circRNA563 promoting hepatocellular carcinoma by targeting the microRNA148a-3p/metal-regulatory transcription factor-1 pathway. World J Gastroenterol 2023; 29(46): 6060-6075 [PMID: 38130740 DOI: 10.3748/wjg.v29.i46.6060]
Corresponding Author of This Article
Zhen Yang, MD, PhD, Doctor, Professor, Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Road, Jinan 250021, Shandong Province, China. yangzhen@sdfmu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
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Basic Study
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Lyu ZZ, Li M, Yang MY, Han MH, Yang Z. Exosome-mediated transfer of circRNA563 promoting hepatocellular carcinoma by targeting the microRNA148a-3p/metal-regulatory transcription factor-1 pathway. World J Gastroenterol 2023; 29(46): 6060-6075 [PMID: 38130740 DOI: 10.3748/wjg.v29.i46.6060]
World J Gastroenterol. Dec 14, 2023; 29(46): 6060-6075 Published online Dec 14, 2023. doi: 10.3748/wjg.v29.i46.6060
Exosome-mediated transfer of circRNA563 promoting hepatocellular carcinoma by targeting the microRNA148a-3p/metal-regulatory transcription factor-1 pathway
Zhuo-Zhen Lyu, Meng Li, Ming-Yu Yang, Mei-Hong Han, Zhen Yang
Zhuo-Zhen Lyu, Meng Li, Ming-Yu Yang, Mei-Hong Han, Zhen Yang, Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
Author contributions: Yang Z designed and coordinated the study, and wrote the manuscript; Lyu ZZ, Li M, Yang MY, and Han MH performed the experiments; Lyu ZZ, Li M, Han MH, and Yang Z acquired and analyzed the data; Lyu ZZ, Han MH, and Yang Z interpreted the data; and all authors approved the final version of the article.
Supported bythe National Natural Science Foundation of China, No. 81972606 and 82271774.
Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Medical Ethics Committee of Shandong Provincial Hospital (protocol code NSFC: NO.2019-012; date of approval: 02/19/2019).
Institutional animal care and use committee statement: The animal study was approved by the Animal Ethics Committee of Shandong Provincial Hospital (protocol code NSFC: NO.2019-021; approval date: 02/19/2019).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets used and/or analyzed during the present study are available from the corresponding author upon reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Corresponding author: Zhen Yang, MD, PhD, Doctor, Professor, Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Road, Jinan 250021, Shandong Province, China. yangzhen@sdfmu.edu.cn
Received: September 29, 2023 Peer-review started: September 29, 2023 First decision: October 16, 2023 Revised: October 24, 2023 Accepted: November 17, 2023 Article in press: November 17, 2023 Published online: December 14, 2023 Processing time: 74 Days and 18.5 Hours
ARTICLE HIGHLIGHTS
Research background
Mesenchymal stem cells (MSCs) exert anti-oncogenic effects via exosomes containing non-coding RNA (ncRNA), and the efficacy of MSC-derived exosome therapies has been demonstrated. Our preliminary study identified the interaction of the ncRNA hsa_circ_0000563 (circ563) and the circ563-associated miR-148a-3p which are both enclosed in exosomes, as miR-148a-3p and its target metal-regulatory transcription factor-1 (MTF-1) are implicated in hepatocellular carcinoma (HCC) progression.
Research motivation
This study is to identify the clinical significance, functional implications, and mechanisms of circ563 in HCC.
Research objectives
This study aims to investigate the role of circ563 in modulating HCC functions.
Research 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 miRNA of circ563, whose role in HCC regulation was assessed in vitro and in vivo.
Research results
Circ563 silencing blocked the HCC cell proliferation and invasion and induced apoptosis. Co-culturing of HCC cells with MSC-derived exosomes following circ563 overexpression contributed to 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 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.
Research conclusions
Our findings suggested MSCs may exhibit anti-HCC activity through the exosomal circ563/miR-148a-3p/MTF-1 pathway.
Research perspectives
The study presents a new dataset related to HCC. We clarified the regulatory mechanisms of circ563, which can sponge miR-148a-3p to elicit MTF-1-dependent oncogenic effects in HCC. Thus, the ncRNA circ563 could be a potential therapeutic target, and liquid biopsy of serum exosomes targeting circ563 may help predict the prognosis of patients with HCC.
