image: Image Caption: The epigenetic regulatory network of lncRNAs in hepatocellular carcinoma. Image link: https://ars.els-cdn.com/content/image/1-s2.0-S2352304225000236-gr1_lrg.jpg
Credit: Genes & Diseases
A new review published in Genes & Diseases explores the intricate epigenetic regulatory network of long noncoding RNAs (lncRNAs) in hepatocellular carcinoma (HCC), shedding light on the profound impact of DNA methylation, histone modifications, RNA methylation, and microRNAs on lncRNA transcription. This analysis highlights how these regulatory mechanisms drive the progression of liver cancer, offering valuable insights for future diagnostic and therapeutic strategies.
The role of lncRNAs in cancer biology has become increasingly evident, as they regulate gene expression, chromatin remodeling, and cellular signaling pathways. In HCC, these molecules interact with epigenetic modifiers to influence tumor growth, metastasis, and resistance to therapy. The review delves into how DNA methylation silences tumor-suppressing lncRNAs, while histone modifications either promote or inhibit their expression depending on the nature of methylation or acetylation. Additionally, RNA methylation—particularly N6-methyladenosine (m6A) modification—emerges as a crucial mechanism altering the stability and translation of these transcripts.
Beyond direct modifications, microRNAs (miRNAs) play a pivotal role in fine-tuning lncRNA expression through post-transcriptional regulation. The interplay between miRNAs and lncRNAs creates a complex competing endogenous RNA network, impacting key oncogenic and tumor-suppressive pathways in HCC.
Understanding these epigenetic interactions opens avenues for novel biomarkers that could revolutionize early detection, prognosis, and treatment approaches. The identification of epigenetically regulated lncRNAs paves the way for targeted therapies that modulate their function, potentially overcoming drug resistance and enhancing therapeutic efficacy.
This review offers a deeper comprehension of how lncRNA-driven epigenetic regulation contributes to HCC pathogenesis. These insights provide a foundation for developing innovative RNA-based therapies aimed at disrupting cancer-promoting networks while preserving essential cellular functions.
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Reference
Zhaoqi Shi, Shengxi Jin, Xiaolong Liu, Mengting Jiang, Yifeng Fang, Parikshit Asutosh Khadaroo, Hui Lin, Xiaoxiao Fan, The epigenetic regulatory network of long noncoding RNAs in hepatocellular carcinoma, Genes & Diseases, Volume 12, Issue 5, 2025, 101534, https://doi.org/10.1016/j.gendis.2025.101534
Funding Information:
National Natural Science Foundation of China U23A20487
National Natural Science Foundation of China 82001874
National Natural Science Foundation of China 82102105
Zhejiang Engineering Research Center of Cognitive Healthcare (China) 2017E10011
Natural Science Foundation of Zhejiang Province, China LQ22H160017
Zhejiang Province Science and Technology Plan Project (China) 2022C03134
Science and Technology Innovation 2030 Plan Project of China 2022ZD0160703
Journal
Genes & Diseases