Fig 2: The long non-coding RNA HHIP-AS1 is a hallmark of human SHH-driven tumors.a Long non-coding RNA (lncRNA) expression profiles in SHH-driven medulloblastoma (MB; right side) versus non SHH-driven MB (left side). The volcano plot illustrates the distribution of statistical significance (y-axis) and relative expression level (x-axis) for the lncRNAs profile. The red dot indicates HHIP-AS1 (HedgeHog Interacting Protein-Anti-Sense 1). Statistical analysis was performed using one-way ANOVA with post-hoc Tukey HSD; ***p < 0.001. b Violin plots display the expression level of HHIP-AS1 according to an integrative transcriptomic analysis of 3492 samples from neoplastic brain tissues with SHH activation (SHH MB and atypical teratoid/rhabdoid tumors (ATRT)) or without commonly reported SHH activation (brain tumors) and normal brain without tumor. Statistical analysis was performed using Kruskal–Wallis Test with Dunn’s Multiple Comparison Test; ***p < 0.001. Red dots = SHH-driven entities; black dots = non SHH-driven tumors and control tissue. c H3K27ac ChIP-sequencing profile on HHIP-AS1 and HHIP loci in the four MB subgroups64. Bar graph indicates the expression level of HHIP-AS1 in the corresponding MB subgroups. Error bars represent ± SEM. d Scatter plot representing the degree of DNA methylation (B value) of the potential promoter region in relation to HHIP-AS1 expression levels in SHH MB (red dots) and other MB subgroups (black dots). Statistics were done by Pearson correlation. e Scatter plot displaying expression correlation of HHIP and HHIP-AS1 across datasets (n = 351). Mean expressions of both transcripts from 39,090 samples were analyzed in their respective datasets and plotted with error bars representing the SEM for both genes. Statistics were done by Pearson correlation. f The bar graph indicates the relative luciferase activity of empty luciferase vector (pLUC) or pLUC containing the cloned HHIP promoter sequence orientation (fw = forward, rv = reversed). The results are presented as the mean ± SD of three independent experiments. Student´s two-sided t-test; **p < 0.01, ***p < 0.001. g Identification of evolutionarily conserved regions corresponding to critical regulatory elements in large (>1 Mb), highly conserved gene desert regions flanking the human HHIP-AS1 gene located at chromosome 4q31.21 with two exons. Source data and exact p-values are provided as a “Source Data file”.