SRP230803 PRJNA590733 GSE140741 The lncRNA HHIP-AS1 is required for oncogenic SHH signaling in humans Here we show that the non-conserved lncRNA HHIP-AS1 promotes tumorigenesis in human SHH-driven brain tumors, including medulloblastoma, atypical teratoid / rhabdoid tumors (AT/RT). We reveal that GLI2 regulates a bidirectional promoter shared between the well-characterized SHH regulator HHIP and HHIP-AS1. We found a novel regulatory lncRNA mechanism, termed blocking endogenous RNA (beRNA), extending the concept of competing endogenous RNA (ceRNA), where HHIP-AS1 binds its target DYCN1I2 to avoid miRNA-425-based degradation. Overall design: HHIP-AS1 knockdown GSE140741