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Enhancer RNA of the NEAT1-MALAT1 locus (eNEMAL) is a polyadenylated, 762 nucleotide-long noncoding RNA transcribed from an enhancer region situated approximately 30 kb downstream of the NEAT1 gene and 20 kb upstream of the MALAT1 gene on human chromosome 11q13.1. eNEMAL is upregulated by hypoxic conditions in multiple breast cancer cell lines, but not in non-tumorigenic cells. Functionally, eNEMAL influences the expression of NEAT1 isoforms in breast cancer cells by promoting the long, non-polyadenylated isoform (NEAT1_2) at the expense of the short polyadenylated NEAT1_1 isoform, likely by inhibiting the 3’-end polyadenylation required for NEAT1_1 production. The specific role of eNEMAL in gene regulation highlights the importance of enhancer RNAs in modulating alternative RNA processing events relevant to cancer biology and hypoxia adaptation. No current evidence suggests that eNEMAL itself is a direct therapeutic target, nor are there known drugs that interact directly with it[1]. Furthermore, eNEMAL requires further experimental validation to resolve whether observed effects on NEAT1_2 are direct or potentially involve off-target effects by siRNAs, indicating that caution is advised when interpreting its mechanistic significance[1].
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