Hedgehog interacting protein antisense RNA 1 (HHIP-AS1)

Hedgehog interacting protein antisense RNA 1 (HHIP-AS1) is a primate-specific long non-coding RNA (lncRNA) transcribed from a bidirectional promoter shared with the HHIP gene, a regulator of Sonic Hedgehog (SHH) signaling. HHIP-AS1 serves regulatory roles in human cancers, notably SHH-driven tumors and non-small cell lung cancer, by modulating the stability and expression of HHIP and other mRNAs such as DYNC1I2. Knockdown of HHIP-AS1 impairs tumor growth, cell proliferation, and induces mitotic spindle deregulation, while overexpression can inhibit cellular stemness, EMT, migration, and invasion in specific contexts. HHIP-AS1 stabilizes the HHIP and DYNC1I2 RNAs, interfering with microRNA-mediated degradation, and represses the Hedgehog pathway by enhancing HHIP expression and its stability via protein partners like CELF2 and ELAVL1. HHIP-AS1 is recognized as a therapeutic target and a biomarker for prognosis in cancers, though direct pharmacological targeting has yet to be described in detail. Its functional role is human-specific, with no direct evolutionary conservation in rodent models.

Other names

HHIP-AS1Hedgehog interacting protein antisense RNA 1HHAS1HHIP antisense RNA 1 (non-protein coding)

Drugs targeting HHIP-AS1 would likely act via modulation of lncRNA expression or interference with its interactions (e.g., with HHIP, DYNC1I2, or miRNAs), thus indirectly affecting Hedgehog signaling, cell proliferation, EMT, or stemness