Deng Y, Yan L. RNA-centered mechanisms sustaining self-renewal in hepatocellular carcinoma stem cells: Effector dosage, protein output and regulatory deployment. World J Stem Cells 2026; 18(9): 125599 [DOI: 10.4252/wjsc.125599]
Corresponding Author of This Article
Yi Deng, MD, Department of Oncology, The Second Xiangya Hospital of Central South University, No. 139 Renmin Middle Road, Changsha 410011, Hunan Province, China. dengyi@csu.edu.cn
Research Domain of This Article
Oncology
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review-article
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Deng Y, Yan L. RNA-centered mechanisms sustaining self-renewal in hepatocellular carcinoma stem cells: Effector dosage, protein output and regulatory deployment. World J Stem Cells 2026; 18(9): 125599 [DOI: 10.4252/wjsc.125599]
World J Stem Cells. Sep 26, 2026; 18(9): 125599 Published online Sep 26, 2026. doi: 10.4252/wjsc.125599
RNA-centered mechanisms sustaining self-renewal in hepatocellular carcinoma stem cells: Effector dosage, protein output and regulatory deployment
Yi Deng, Long Yan
Yi Deng, Long Yan, Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China
Co-first authors: Yi Deng and Long Yan.
Author contributions: Deng Y and Yan L drafted the manuscript as co-first authors; Deng Y developed the initial concept and framework for the manuscript and revised the manuscript. Both of the two authors contributed to the content and critical review of the manuscript, and approved the final version to publish.
AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Yi Deng, MD, Department of Oncology, The Second Xiangya Hospital of Central South University, No. 139 Renmin Middle Road, Changsha 410011, Hunan Province, China. dengyi@csu.edu.cn
Received: July 14, 2026 Revised: August 12, 2026 Accepted: September 11, 2026 Published online: September 26, 2026 Processing time: 75 Days and 18.6 Hours
Abstract
Hepatocellular carcinoma (HCC) stem cells sustain tumor propagation, relapse and treatment tolerance. However, the RNA-dependent mechanisms preserving their self-renewal remain scattered across studies of miRNAs, lncRNAs, circRNAs, snoRNAs, RNA-binding proteins and RNA-processing enzymes. Here, we examine how RNA molecules and RNA-processing machineries maintain functional self-renewal by controlling self-renewal effectors. Rather than cataloging RNA classes, we organize the evidence by molecular operation. RNA mechanisms first tune effector dosage and availability through transcript repression, stabilization, export, translational access and protein turnover. They also specify protein output through m6A regulation, RNA editing, ribosome biogenesis, tRNA modification and transcript-selective translation. A third layer deploys regulatory activity by directing protein localization, partner choice and locus access. These operations converge on NOTCH, Wnt-β-catenin, Hedgehog/GLI1, Hippo-YAP and TGF-β/IL-6-STAT3 signaling, but pathway-level convergence does not establish a universal RNA program. We emphasize evidence from serial propagation, limiting dilution, genetic perturbation and rescue, and distinguish functional self-renewal from marker enrichment, sphere formation or tumor shrinkage. Current evidence supports state-specific RNA dependencies in defined HCC stem-cell models, but their universality across HCC subtypes and selectivity over normal liver regeneration remain unresolved.
Core Tip: Here, we examine how RNA molecules and RNA-processing machineries maintain functional self-renewal by controlling self-renewal effectors. Rather than cataloging RNA classes, we organize the evidence by molecular operation. RNA mechanisms first tune effector dosage and availability through transcript repression, stabilization, export, translational access and protein turnover.
