Mehra Nikita, Sundaram Subhiksha, Shah Parth, Rao Arunagiri Kuha Deva Magendhra
Department of Medical Oncology & Molecular Oncology, Cancer Institute (WIA), Chennai, TN, India.
Department of Pathology and Lab Medicine, Dartmouth Hitchcock Medical Center, Hanover, NH, USA.
Curr Oncol Rep. 2025 Jan;27(1):37-44. doi: 10.1007/s11912-024-01623-5. Epub 2025 Jan 3.
This review aims to explore the pivotal role of long non-coding RNAs (lncRNAs) as epigenetic regulators in the pathogenesis of multiple myeloma (MM). Additionally, we have portrayed the dual role of lncRNAs in the epigenetic landscape of MM pathobiology.
In MM, lncRNAs are pivotal for proliferation, progression, and drug resistance by acting as miRNA sponges, regulating mRNA activity through microRNA recognition elements (MREs). Epigenetic modifications in lncRNAs influence gene expression, with some like MEG3, GAS5, CRNDE, and H19 showing promoter hypermethylation, while MALAT1 exhibits hypomethylation. Targeting lncRNAs using siRNA, ASO, CRISPR-Cas9, or small molecule inhibitors shows promise in preclinical studies, alongside the potential benefits of epigenetic-based therapies such as DNMTi and HDACi. Clinical trials combining epigenetic modifiers with standard chemotherapy show encouraging results, especially in relapsed/refractory MM. The key finding of the studies highlighted in the review paves the way for understanding the epigenetic role of lncRNAs in MM disease progression and biology. In addition, the novel therapeutic strategies that have shown promising results have been highlighted. The adoption of the epigenetic landscape into therapeutics in addition to existing treatment strategies may increase the efficacy of treatment approaches.
本综述旨在探讨长链非编码RNA（lncRNA）作为表观遗传调节因子在多发性骨髓瘤（MM）发病机制中的关键作用。此外，我们还描述了lncRNA在MM病理生物学表观遗传格局中的双重作用。
在MM中，lncRNA通过充当miRNA海绵、通过微小RNA识别元件（MRE）调节mRNA活性，对增殖、进展和耐药性起关键作用。lncRNA中的表观遗传修饰影响基因表达，一些如MEG3、GAS5、CRNDE和H19表现出启动子高甲基化，而MALAT1表现出低甲基化。在临床前研究中，使用小干扰RNA（siRNA）、反义寡核苷酸（ASO）、CRISPR-Cas9或小分子抑制剂靶向lncRNA显示出前景，同时基于表观遗传学的疗法如DNA甲基转移酶抑制剂（DNMTi）和组蛋白去乙酰化酶抑制剂（HDACi）也有潜在益处。将表观遗传修饰剂与标准化疗相结合的临床试验显示出令人鼓舞的结果，尤其是在复发/难治性MM中。本综述中强调的研究的关键发现为理解lncRNA在MM疾病进展和生物学中的表观遗传作用铺平了道路。此外，还强调了已显示出前景的新型治疗策略。除现有治疗策略外，将表观遗传格局应用于治疗可能会提高治疗方法的疗效。
