The long noncoding RNA lnc-HLX-2-7 is oncogenic in Group 3 medulloblastomas

• DOI: 10.1093/neuonc/noaa235
• Publication Date: 2020-10-13T19:31:12Z
• Authors: Keisuke Katsushima; Bongyong Lee; Haritha Kunhiraman; Cuncong Zhong; Rabi Murad; Jun Yin; Ben Liu; Alexandra Garancher; Ignacio Gonzalez-...; Hector L Monforte; Stacie Stapleton; Rajeev Vibhakar; Chetan Bettegowda; Robert J Wechsler...; George Jallo; Eric Raabe; Charles G Eberhart; Ranjan J Perera
• Keywords: Identification

Abstract Background Medulloblastoma (MB) is an aggressive brain tumor that predominantly affects children. Recent high-throughput sequencing studies suggest the noncoding RNA genome, in particular long RNAs (lncRNAs), contributes to MB subgrouping. Here we report identification of a novel lncRNA, lnc-HLX-2-7, as potential molecular marker and therapeutic target Group 3 MBs. Methods Publicly available (RNA-seq) data from 175 patients were interrogated identify lncRNAs differentiate between subgroups. After characterizing subset differentially expressed vitro vivo, lnc-HLX-2-7 was deleted by CRISPR/Cas9 cell line. Intracranial injected tumors further characterized bulk single-cell RNA-seq. Results Lnc-HLX-2-7 highly upregulated lines, patient-derived xenografts, primary MBs compared with other subgroups assessed quantitative real-time, RNA-seq, fluorescence situ hybridization. Depletion significantly reduced proliferation 3D colony formation induced apoptosis. Lnc-HLX-2-7–deleted cells into mouse cerebellums produced smaller than those derived parental cells. Pathway analysis revealed modulated oxidative phosphorylation, mitochondrial dysfunction, sirtuin signaling pathways. The MYC oncogene regulated small-molecule bromodomain extraterminal domain family‒bromodomain 4 inhibitor Jun Qi 1 (JQ1) expression. Conclusions oncogenic represents promising