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TSPEAR antisense RNA 1 (TSPEAR-AS1)

Target
TSPEAR-AS1
Molecular classification
Long non-coding RNA (lncRNA), Other
01

Overview

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]

Other names
C21orf31C21orf90TSPEAR-AS2TSPEAR antisense RNA 1 (non-protein coding)
02

Mechanism of action

RNA interference (knockdown with antisense oligonucleotides leading to down-regulation of oncogenic lncRNA function)

03

Biological functions

Regulation of gene expressionModulation of interferon signalingPromotion of cell proliferationCell cycle progressionMigrationStemness regulation
04

Disease associations

Cancer (notably esophageal cancer)Possible biomarkers in other solid tumorsTooth agenesisDeafness
05

Safety considerations

Potential challenges around delivery and off-target effects of lncRNA-directed therapeuticsUncertain effects in normal tissues due to limited specificity studies
06

Interacting drugs

Antisense oligonucleotides targeting TSPEAR-AS2 (for experimental inhibition)
07

Biomarkers

High TSPEAR-AS2 expression (prognostic biomarker for esophageal cancer with association to poor survival)Possible biomarker for early diagnosis and prognostic evaluation in esophageal squamous cell carcinoma

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