LncRNA-Histone Modification Crosstalk: Orchestrating Cancer Pathobiology

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.