A therapeutically targetable positive feedback loop between lnc-HLX-2-7, HLX, and MYC that promotes group 3 medulloblastoma

• DOI: 10.1016/j.celrep.2024.113938
• Publication Date: 2024-03-08T22:05:57Z
• Authors: Keisuke Katsushima; Kandarp Joshi; Menglang Yuan; Brigette Romero; Mona Batish; Stacie Stapleton; George Jallo; Elayaraja Kolanthai; Sudipta Seal; Olivier Saulnier; Michael D. Taylor; Robert J. Wechsle...; Charles G. Eberhart; Ranjan J. Perera
• Keywords: Positive feedback

Recent studies suggest that long non-coding RNAs (lncRNAs) contribute to medulloblastoma (MB) formation and progression. We have identified an lncRNA, lnc-HLX-2-7, as a potential therapeutic target in group 3 (G3) MBs. lnc-HLX-2-7 RNA specifically accumulates the promoter region of HLX, sense-overlapping gene which activates HLX expression by recruiting multiple factors, including enhancer elements. sequencing chromatin immunoprecipitation reveal binds promoters several oncogenes, TBX2, LIN9, HOXM1, MYC. Intravenous treatment with cerium-oxide-nanoparticle-coated antisense oligonucleotides targeting (CNP-lnc-HLX-2-7) inhibits tumor growth 40%–50% intracranial MB xenograft mouse model. Combining CNP-lnc-HLX-2-7 standard-of-care cisplatin further significantly prolongs survival compared monotherapy. Thus, lnc-HLX-2-7-HLX-MYC axis is important for regulating G3 progression, providing strong rationale using