Maternally Expressed Gene 3 (MEG3) LncRNA: The silent guardian against solid and hematological malignancies.

Maternally Expressed Gene 3 (MEG3), a long non-coding RNA (lncRNA) that plays a crucial role in regulating cellular processes, including apoptosis, proliferation, and tumor suppression. MEG3 is located at the DLK1-MEG3 locus on human chromosome 14q32.3 and is implicated in multiple cancers and pathological conditions. MEG3 expression is often downregulated in various solid and liquid malignancies due to promoter hypermethylation, leading to tumor progression and poor prognosis. Yet, it showed paradoxical expression in other malignancies. MEG3 interacts with multiple molecular pathways, including p53, NF-κB, EZH2, and miRNAs, influencing gene expression and cellular responses. Recent studies highlight its role as a competing endogenous RNA (ceRNA), modulating miRNAs activity to regulate oncogenic-related target genes. MEG3 has been identified as a potential therapeutic agent in breast cancer, glioblastoma, neuroblastoma, and osteosarcoma, where its restoration inhibits tumor growth, metastasis, and drug resistance. Additionally, MEG3 contributes to epigenetic regulation, chromatin remodeling, and metabolic reprogramming in cancer cells. Its tumor-suppressive functions make it a promising biomarker for cancer diagnosis and prognosis, as well as a candidate for targeted therapies. Despite extensive research, the precise molecular mechanisms underlying MEG3 function remain incompletely understood, underscoring the need for further studies to explore its therapeutic potential in oncology and other diseases.