Letter to the Editor Open Access
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2024; 30(17): 2369-2370
Published online May 7, 2024. doi: 10.3748/wjg.v30.i17.2369
Targeting therapy for hepatocellular carcinoma by delivering microRNAs as exosomal cargo
Takeshi Suda, Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami Uonuma 949-7302, Niigata, Japan
ORCID number: Takeshi Suda (0000-0002-8231-0883).
Author contributions: Suda T read the review article by Wang et al and wrote this entire letter to the editor.
Conflict-of-interest statement: The author declares he has no conflicts of interest in relation to this letter.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Takeshi Suda, MD, PhD, Professor, Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, 4132 Urasa, Minami Uonuma 949-7302, Niigata, Japan. tspitt@med.niigata-u.ac.jp
Received: January 20, 2024
Revised: March 6, 2024
Accepted: April 11, 2024
Published online: May 7, 2024


Exosomes, the smallest extracellular vesicles, have gained significant attention as key mediators in intercellular communication, influencing both physiological and pathological processes, particularly in cancer progression. A recent review article by Wang et al was published in a timely manner to stimulate future research and facilitate practical developments for targeted treatment of hepatocellular carcinoma using exosomes, with a focus on the origin from which exosomes derive. If information about the mechanisms for delivering exosomes to specific cells is incorporated, the concept of targeted therapy for hepatocellular carcinoma using exosomes could be more comprehensively understood.

Key Words: Exosomal delivery, Therapeutic targets, MicroRNAs, Hepatocellular carcinoma

Core Tip: Wang et al thoroughly explored the functions and biomedical significance of exosomal microRNAs transferred by both parenchymal and nonparenchymal cells in the framework of potential therapeutic targets for hepatocellular carcinoma. This review aimed to do more than just summarize the role of microRNAs in hepatocarcinogenesis. It also sought to illuminate the process of cellular communication using exosomal microRNA cargo. Therefore, it would be beneficial for the review to include information on how this cargo is delivered to target cells.


We have read the original review article titled 'Function and biomedical implications of exosomal microRNAs delivered by parenchymal and nonparenchymal cells in hepatocellular carcinoma' by Wang et al[1], published in the October issue of World Journal of Gastroenterology. We would like to extend our congratulations to the authors for this informative article and offer some suggestions.

Following an introduction to exosomes regarding their formation, composition, and function, this review briefly summarizes the crucial role of microRNAs in hepatocarcinogenesis. Subsequently, the direct and indirect effects of various microRNAs carried by exosomes on hepatocellular carcinoma cells, such as hepatic stellate cells, cancer-associated fibroblasts, adipocytes, vascular endothelial cells, and immune cells of different types, are systematically categorized based on their origin. Finally, the authors list potential therapeutic applications of microRNA delivery through exosomes.

Most of this review is dedicated to listing examples of microRNAs involved in the development and progression of hepatocellular carcinoma. This review effectively illustrates which types of cells deliver specific microRNAs to communicate with hepatocellular carcinoma cells. In the concluding discussion, the authors explore the potential applications of microRNAs in the treatment of hepatocellular carcinoma using exosomes; however, there is no information provided on how the released exosomes will reach their target cells.

While exosomes theoretically have the ability to be delivered to various cell types, targeted delivery to specific cell types has been observed and achieved through the engineering of specific exosomes. Lima et al[2] reported that cytokines in tumor interstitial fluid bind to cancer exosomes and determine their biodistribution based on cytokine receptor expression. Liang et al[3] summarized the current knowledge of exosome engineering through genetic and chemical methods for targeted drug delivery.

The current review proposes targeted therapy for hepatocellular carcinoma using exosomal delivery of microRNAs. Understanding the specific exosome delivery mechanisms would significantly advance the development of more precise and effective therapies for hepatocellular carcinoma.


Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Gastroenterology and hepatology

Country/Territory of origin: Japan

Peer-review report’s classification

Scientific Quality: Grade B

Novelty: Grade B

Creativity or Innovation: Grade B

Scientific Significance: Grade B

P-Reviewer: Tchilikidi KY, Russia S-Editor: Fan JR L-Editor: A P-Editor: Yu HG

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2.  Lima LG, Ham S, Shin H, Chai EPZ, Lek ESH, Lobb RJ, Müller AF, Mathivanan S, Yeo B, Choi Y, Parker BS, Möller A. Tumor microenvironmental cytokines bound to cancer exosomes determine uptake by cytokine receptor-expressing cells and biodistribution. Nat Commun. 2021;12:3543.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 18]  [Cited by in F6Publishing: 69]  [Article Influence: 23.0]  [Reference Citation Analysis (0)]
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