INTEGRATED ANALYSIS REVEALS LONG NON-CODING RNA–MEDIATED EPIGENETIC AND TRANSCRIPTIONAL REGULATORY NETWORKS IN HAEMATOLOGICAL MALIGNANCIES

Abstract

Long non-coding RNAs (lncRNAs) play critical roles in regulating gene expression through epigenetic and transcriptional mechanisms and have emerged as important contributors to the development of hematological malignancies. However, the integrated regulatory networks mediated by lncRNAs remain incompletely understood. An integrated multi-omics bioinformatics approach was employed using publicly available transcriptomic and clinical datasets to identify differentially expressed lncRNAs and investigate their functional, epigenetic, immune, and clinical significance. Differential expression, functional enrichment, lncRNA–mRNA co-expression, competing endogenous RNA (ceRNA) network construction, immune infiltration analysis, survival analysis, and external dataset validation were performed. The analysis identified MALAT1, PVT1, HOTAIR, NEAT1, H19, MEG3, and GAS5 as key regulatory lncRNAs associated with hematological malignancies. Functional enrichment revealed significant involvement of the PI3K–AKT, JAK–STAT, MAPK, NF-κB, Wnt/β catenin, and p53 signaling pathways. Epigenetic analyses demonstrated strong associations with DNA methylation, histone modifications, and chromatin remodeling, while immune analysis indicated significant correlations with immune cell infiltration and immune checkpoint expression. Independent validation confirmed the reproducibility and prognostic value of the identified lncRNA signature. These findings demonstrate that lncRNAs serve as central regulators of epigenetic remodeling, transcriptional regulation, immune modulation, and disease progression in hematological malignancies, highlighting their potential as novel diagnostic, prognostic, and therapeutic biomarkers for precision oncology.