Epigenetic Role of Long Non-coding RNAs in Multiple Myeloma

Purpose of the review: 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.

Recent findings: 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.