HNF1A antisense RNA 1 (HNF1A-AS1)

HNF1A antisense RNA 1 (HNF1A-AS1) is an evolutionarily conserved, nuclear long noncoding RNA expressed specifically in tissues where HNF1A is present (liver, pancreas, gut, kidney). It is transcribed in an antisense orientation from the HNF1A locus, originating from a promoter region called HASTER. HNF1A-AS1 functions primarily as a cis-regulatory element: its promoter modulates HNF1A expression by sensing HNF1A concentrations, thus providing both activating and inhibitory feedback to fine-tune transcription. The presence or absence of HNF1A-AS1 can lead to loss or overexpression of HNF1A, and disruption impacts both metabolic function and cellular proliferation. Functionally, HNF1A-AS1 is involved in the regulation of cytochrome P450 enzymes in the liver, thus affecting drug metabolism and potentially the toxicity of pharmaceuticals. It also interacts with a multitude of molecules, including miRNAs (acting as a sponge) and epigenetic modulators (DNMT1, EZH2), further broadening its role in gene regulation. Its dysregulation has been implicated in diabetes and several cancers, where it serves as a prognostic biomarker and is considered a potential therapeutic target, though drug development is still preclinical.

Other names

HNF1A-AS1FLJ38690HAS1HASTERHNF1A stabilizer transcriptsC12orf27NCRNA00262HNF1A antisense RNA 1 (non-protein coding)

Mechanistic relevance is by modulating expression of drug-metabolizing enzymes and possibly by affecting tumor biology via gene regulation, but no approved drugs act directly on HNF1A-AS1.