Jasim Saade Abdalkareem, Pallathadka Harikumar, Hjazi Ahmed, Sanghvi Gaurav, M M Rekha, Agarwal Mohit, Arya Renu, Alasheqi Mohammed Qasim, Kadhim Abed J, Kariem Muthena
Medical Laboratory Techniques Department, College of Health and Medical Technology, University of Al-Maarif, Anbar, Iraq.
Manipur International University, Imphal, Manipur, India.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul 11. doi: 10.1007/s00210-025-04402-6.
Long noncoding RNAs (lncRNAs) and histone modifications are key epigenetic regulators in cancer pathobiology. This review delves into the crosstalk between lncRNAs and histone modifications relevant to tumor initiation and development in a detailed manner. Histone modifications (e.g., methylation, acetylation, phosphorylation, and ubiquitination) play key roles in chromatin structure and gene expression, involved in such cellular processes as proliferation, metastasis, and drug resistance. These lncRNAs have a variety of mechanisms of action, such as signaling, scaffolding, decoying, and guiding to modify critical cellular pathways. They recruit histone methyltransferases, demethylases, acetyltransferases, and deacetylases to specific regions of genomic transcription regulation, thereby changing certain histone-modifying marks that affect gene expression. The abnormal expression and activities of lncRNAs such as HOTAIR, MALAT1, LINC00152, and SNHG1 are associated with tumor initiation, progression, and metastasis in various cancers. Therefore, these molecules are candidates for diagnostic and prognostic biomarkers, making non-invasive detection and prediction possible. LncRNA-related histone modifications also serve as an attractive candidate for future therapeutic targets in cancer. Antisense oligonucleotides, small molecule inhibitors, and RNA interference are some of the strategies currently being investigated to dislodge the interactions between lncRNAs and histone-modifying enzymes, and they represent novel strategies for cancer therapy. This review summarizes recent advances in understanding lncRNA-histone modification crosstalk and its translation to the clinic for precision oncotherapy.
长链非编码RNA（lncRNAs）和组蛋白修饰是癌症病理生物学中的关键表观遗传调节因子。本综述详细探讨了lncRNAs与组蛋白修饰之间与肿瘤发生和发展相关的相互作用。组蛋白修饰（如甲基化、乙酰化、磷酸化和泛素化）在染色质结构和基因表达中起关键作用，参与细胞增殖、转移和耐药性等细胞过程。这些lncRNAs具有多种作用机制，如信号传导、支架作用、诱饵作用和引导作用，以修饰关键的细胞途径。它们将组蛋白甲基转移酶、去甲基酶、乙酰转移酶和脱乙酰酶招募到基因组转录调控的特定区域，从而改变某些影响基因表达的组蛋白修饰标记。HOTAIR、MALAT1、LINC00152和SNHG1等lncRNAs的异常表达和活性与各种癌症的肿瘤发生、进展和转移相关。因此，这些分子是诊断和预后生物标志物的候选者，使得非侵入性检测和预测成为可能。与lncRNA相关的组蛋白修饰也作为癌症未来治疗靶点的有吸引力的候选者。反义寡核苷酸、小分子抑制剂和RNA干扰是目前正在研究的一些策略，以消除lncRNAs与组蛋白修饰酶之间的相互作用，它们代表了癌症治疗的新策略。本综述总结了在理解lncRNA-组蛋白修饰相互作用及其向精准肿瘤治疗临床转化方面的最新进展。
