KMT2E antisense RNA 1 (KMT2E-AS1)

KMT2E antisense RNA 1 (KMT2E-AS1) is a nuclear-enriched long noncoding RNA located adjacent to the KMT2E gene on the human genome. It forms complexes with and stabilizes KMT2E protein, facilitating increased H3K4me3 histone marks and activating transcriptional programs associated with hypoxia adaptation, cell proliferation, metabolic switching (glycolysis), and endothelial dysfunction. The KMT2E-AS1/KMT2E axis creates a feed-forward loop with HIF-2α, intensifying metabolic and epigenetic disturbances in pulmonary hypertension. Experimental silencing of KMT2E-AS1 or inhibition of its activity in pre-clinical models protects against pulmonary hypertension, positioning it as a promising, though still experimental, therapeutic target. Genetic variants (e.g., rs73184087) modulate its expression and confer disease risk, suggesting biomarker utility in patient stratification. No approved therapies target KMT2E-AS1 directly; current evidence derives from research models using siRNA, antisense oligonucleotides, and pharmacological histone methylation inhibitors. Future development will require careful consideration of safety and specificity due to its epigenetic roles.

Other names

lncPENGLOC100216545RP11-325F22.5.1LHFPL3 antisense RNA 2LINC01004KMT2E antisense RNA 1 (head to head)long intergenic non-protein coding RNA 1004LHFPL3-AS2

Antisense oligonucleotides cause gene silencing by promoting RNA degradation. HIF-2α inhibition (e.g., by belzutifan) blocks downstream effects regulated by the KMT2E-AS1 axis.