This new study published in Genes & Diseases by researchers from Shandong Second Medical University and Wuhan University identifies LINC00862 as a clinically significant tumor suppressor and reveals a bidirectional regulatory loop between LINC00862 and RBM47 that restrains HCC growth and metastasis.

Through comprehensive clinical analyses of paired HCC tissues, the researchers demonstrate that LINC00862 is significantly downregulated in tumors and that reduced expression correlates with larger tumor size, poorer pathological grading, and unfavorable patient survival. Multivariate analyses further established LINC00862 as an independent prognostic factor.

Functional assays confirmed that LINC00862 suppresses hepatoma cell proliferation, migration, invasion, and metastatic colonization in vivo, underscoring its anti-tumor activity.
Mechanistically, transcriptomic and quantitative proteomic profiling identify RNA-binding motif protein 47 (RBM47) as a key downstream effector of LINC00862. RBM47 expression positively correlates with LINC00862 levels in clinical samples and hepatoma cell lines. Rescue experiments further demonstrate that RBM47 is indispensable for mediating the anti-tumor effects of LINC00862.

At the molecular level, the study reveals a striking mode of transcriptional regulation. Nuclear-localized LINC00862 directly binds the RBM47 promoter through Hoogsteen base pairing, forming a DNA–RNA triplex structure at a homopurine-rich region. This interaction enhances RBM47 transcription. Importantly, LINC00862 recruits the chromatin remodeler CHD5 to the RBM47 promoter, forming a multicomponent transcriptional complex that amplifies RBM47 activation. Deletion of the critical binding region on LINC00862 abrogates CHD5 recruitment and eliminates its tumor-suppressive effects, underscoring the functional importance of this triplex-mediated mechanism.

Remarkably, RBM47 reciprocally functions as a transcription factor that directly activates LINC00862 expression by binding to its promoter region. This reciprocal activation establishes a positive feedback loop, sustaining elevated levels of both LINC00862 and RBM47 and reinforcing tumor suppression.
Together, these findings define a novel lncRNA–RBP–chromatin remodeling regulatory circuit in liver cancer. By elucidating the LINC00862–CHD5–RBM47 transcriptional axis, this study expands current understanding of triplex-mediated gene regulation and highlights LINC00862 as a promising prognostic biomarker and potential therapeutic target in hepatocellular carcinoma.


Reference
Title of Original Paper: The role of positive feedback loop between LINC00862 and RBM47 in hepatocellular carcinoma suppression

Journal: Genes & Diseases
Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch.

DOI: https://doi.org/10.1016/j.gendis.2025.101763

Funding Information:

• The National Natural Science Foundation of China (No. 82103166)
• Natural Science Foundation of Shandong Province, China (No. ZR2021QH200, No. ZR2020MH192)
• Youth Innovation Technology Project of Higher School in Shandong Province, China (No. 2022KJ267)
• Research Start-up Funds of Shandong Second Medical University, Shandong, China (No. 04102001, No. 02194001)
• Science and Technology Innovation Cultivation Fund of Zhongnan Hospital of Wuhan University, Wuhan, China (No. znpy201802)

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