Ghorbani Vanan Ahmad, Nami Mohammad Taha, Ghorbaninezhad Farid, Eini Pooya, Bagheri Kamyar, Mohammadlou Maryam, Mohammadi Fatemeh, Tahmasebi Safa, Safarzadeh Elham
Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
Clin Exp Med. 2025 May 25;25(1):173. doi: 10.1007/s10238-025-01711-1.
Hepatocellular carcinoma (HCC) represents a multifaceted and aggressive cancer frequently associated with chronic inflammation and immune cell activation. The pathogenesis of HCC is influenced by a variety of factors such as long non-coding RNAs (lncRNAs). LncRNAs, a significant class of non-coding RNAs, contribute to the intricate nature of the transcriptome and are extensively distributed across various tissues and cell types in mammals. In HCC, these transcripts are crucial not only for deepening our molecular understanding but also for advancing clinical outcomes, as they serve as both oncogenes and tumor suppressors by dysregulating essential genes and signaling pathways. Additionally, macrophage polarization is crucial in HCC tumor progression. The study explores the role of lncRNAs in hepatocellular carcinoma (HCC) and elucidates the specific molecular mechanisms by which key lncRNAs such as HULC and MALAT1 regulate macrophage polarization in the tumor microenvironment. These lncRNAs modulate cytokine profiles and influence immune regulators including IL-10 and TGF-β, steering macrophages toward an M2-like, pro-tumor phenotype that fosters aggressive tumor characteristics and progression. Mechanistically, these transcripts interact with epigenetic modifiers like EZH2 to alter histone modifications and chromatin accessibility, while also stabilizing mRNAs that encode inflammatory mediators, thereby reinforcing an immunosuppressive response. The clinical implications of these findings are substantial. The detection of such lncRNAs in patient samples offers a minimally invasive diagnostic avenue, while their pivotal role in complex immune cell behavior positions them as promising prognostic biomarkers. Moreover, targeting these lncRNAs may lead to innovative therapeutic strategies aimed at disrupting tumor-supportive inflammatory cascades and restoring an effective antitumor immune response. Understanding the intricate interplay between lncRNA-mediated epigenetic regulation and macrophage polarization not only refines our grasp of HCC progression but also opens new pathways for interventions designed to improve patient outcomes.
肝细胞癌（HCC）是一种多方面且侵袭性强的癌症，常与慢性炎症和免疫细胞激活相关。HCC的发病机制受多种因素影响，如长链非编码RNA（lncRNA）。LncRNA是一类重要的非编码RNA，它促成了转录组的复杂性，并广泛分布于哺乳动物的各种组织和细胞类型中。在HCC中，这些转录本不仅对于深化我们的分子理解至关重要，而且对于改善临床结果也很重要，因为它们通过失调关键基因和信号通路，既作为癌基因又作为肿瘤抑制因子发挥作用。此外，巨噬细胞极化在HCC肿瘤进展中至关重要。该研究探讨了lncRNA在肝细胞癌（HCC）中的作用，并阐明了关键lncRNA如HULC和MALAT1在肿瘤微环境中调节巨噬细胞极化的具体分子机制。这些lncRNA调节细胞因子谱，并影响包括IL-10和TGF-β在内的免疫调节因子，引导巨噬细胞向类似M2的促肿瘤表型转变，从而促进侵袭性肿瘤特征和进展。从机制上讲，这些转录本与EZH2等表观遗传修饰因子相互作用，改变组蛋白修饰和染色质可及性，同时还稳定编码炎症介质的mRNA，从而加强免疫抑制反应。这些发现具有重大的临床意义。在患者样本中检测此类lncRNA提供了一种微创诊断途径，而它们在复杂免疫细胞行为中的关键作用使其成为有前景的预后生物标志物。此外，靶向这些lncRNA可能会带来创新的治疗策略，旨在破坏肿瘤支持性炎症级联反应并恢复有效的抗肿瘤免疫反应。了解lncRNA介导的表观遗传调控与巨噬细胞极化之间的复杂相互作用，不仅能完善我们对HCC进展的理解，还为旨在改善患者预后的干预措施开辟了新途径。
