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H19 imprinted maternally expressed transcript (H19) is a long non-coding RNA (lncRNA) located on chromosome 11p15.5, functioning as a key regulator of embryonic development and growth (UniProt, 2024). It is part of an imprinted gene cluster and is expressed exclusively from the maternal allele, with its dysregulation linked to growth disorders like Beckwith-Wiedemann syndrome (Niemitz et al., 2004). In many adult cancers, H19 is significantly upregulated and acts as an oncogene by promoting cell proliferation, invasion, and metastasis through mechanisms such as sponging the let-7 microRNA family and serving as a precursor for miR-675 (Ghanbari et al., 2020; Kallen et al., 2013). Because H19 expression is highly tumor-specific in adults, it serves as a promising therapeutic target and diagnostic biomarker (Zhang et al., 2019). Current drug development efforts include BC-819 (DTA-H19), a plasmid that delivers the Diphtheria toxin A gene under the control of the H19 promoter to selectively kill cancer cells (ClinicalTrials.gov, NCT00826150). Other approaches involve using antisense oligonucleotides or small interfering RNAs to silence H19 expression in various solid tumors (Matouk et al., 2013).
Targeted expression of toxins via the H19 promoter or knockdown of H19 transcript using antisense oligonucleotides or siRNA.
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