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TSPEAR antisense RNA 1 (TSPEAR-AS1) is a long non-coding RNA (lncRNA) gene located on human chromosome 21q22.3 that does not encode a protein[8][9]. Also known as C21orf31, C21orf90, and TSPEAR-AS2, this lncRNA has been implicated in promoting tumorigenesis, especially in esophageal squamous cell carcinoma (ESCA)[2]. TSPEAR-AS1/TSPEAR-AS2 functions by activating the interferon signaling pathway, and its expression is upregulated by the RNA methyltransferase METTL1[2]. High expression levels of TSPEAR-AS2 augment proliferation, cell cycle progression, migration, and stemness of ESCA cells; conversely, knockdown of TSPEAR-AS2 (including via antisense oligonucleotides) suppresses these malignant cellular phenotypes and reduces tumor growth in vivo. Notably, elevated TSPEAR-AS2 is associated with poor patient prognosis in ESCA and is being evaluated as a diagnostic and prognostic biomarker[2]. Additional gene-disease associations include roles in tooth agenesis and hereditary deafness[9]. TSPEAR-AS1 primarily acts via regulation of gene expression and modulation of cell signaling, particularly interferon-related pathways, rather than classic “druggable” target modalities (such as receptor or enzyme activity)[2]. The targeting of this lncRNA with nucleic acid drugs is in preclinical exploration; no approved small molecules or biologics target TSPEAR-AS1 at present. Key features: - Non-protein-coding, classified as lncRNA - Mechanistically linked to cancer cell growth and immune modulation via interferon signaling - Experimental targeting via antisense oligonucleotides shows therapeutic potential in preclinical models of esophageal cancer - Safety and clinical efficacy remain to be established, with delivery and specificity as ongoing challenges[2][9]
RNA interference (knockdown with antisense oligonucleotides leading to down-regulation of oncogenic lncRNA function)
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