{"doi":"10.1101/2020.06.08.140251","title":"The long non-coding RNA <i>lnc-HLX-2-7</i> is oncogenic in group 3 medulloblastomas","abstract":"Abstract Background Medulloblastoma (MB) is an aggressive brain tumor that predominantly affects children. Recent high-throughput sequencing studies suggest that the non-coding RNA genome, in particular long non-coding RNAs (lncRNAs), contributes to MB sub-grouping. Here we report the identification of a novel lncRNA, lnc-HLX-2-7 , as a potential molecular marker and therapeutic target in group 3 MBs. Methods Publicly available RNA sequencing (RNA-seq) data from 175 MB patients were interrogated to identify lncRNAs that differentiate between MB subgroups. After characterizing a subset of differentially expressed lncRNAs in vitro and in vivo , the group 3-enriched lncRNA lnc-HLX2-7 was deleted by CRISPR/Cas9 in the MB cell line D425 Med. Intracranially injected tumors were further characterized by bulk and single-cell RNA-sequencing. Results lnc-HLX-2-7 is highly upregulated in group 3 MB cell lines, patient-derived xenografts, and primary MBs compared to other MB sub-groups as assessed by qRT-PCR, RNA-seq, and RNA fluorescence in situ hybridization (FISH). Depletion of lnc-HLX-2-7 with antisense oligonucleotides or CRISPR/Cas9 significantly reduced cell proliferation and 3D colony formation and induced apoptosis. lnc-HLX-2-7-deleted D425 Med cells injected into mouse cerebella produced smaller tumors than those derived from parental cells. Pathway analysis revealed that lnc-HLX2-7 modulated oxidative phosphorylation, mitochondrial dysfunction, and sirtuin signaling pathways. The MYC oncogene regulated lnc-HLX-2-7 , and the small molecule BET-bromodomain (BRD4) inhibitor JQ1 reduced lnc-HLX2-7 expression. Conclusions lnc-HLX-2-7 is oncogenic in MB and represents a promising novel molecular marker and a potential therapeutic target in group 3 MBs in children. Key points lnc-HLX-2-7 is highly upregulated in group 3 medulloblastomas compared to other sub-groups. In vitro and in vivo studies strongly support an oncogenic role for lnc-HLX2-7 in group 3 medulloblastoma. lnc-HLX-2-7 may be a novel biomarker and a potential therapeutic target in group 3 medulloblastoma. Importance of the study Group 3 medulloblastomas are associated with poor clinical outcomes, are difficult to subtype clinically, and their biology is poorly understood. In an effort to address these problems, we identified a group 3-specific long non-coding RNA, lnc-HLX-2-7 , in an in silico analysis of 175 medulloblastomas and confirmed its expression in group 3 medulloblastoma cell lines, patient-derived xenografts, and FFPE samples. CRISPR/Cas9 deletion and antisense oligonucleotide knockdown of lnc-HLX-2-7 significantly reduced cell growth and 3D colony formation and induced apoptosis. Deletion of lnc-HLX-2-7 in cells injected into mouse cerebellums reduced tumor growth compared to parental cells, and RNA sequencing of these tumors revealed lnc-HLX-2-7 -associated modulation of cell viability and cell death signaling pathways. The oncogene MYC regulates lnc-HLX-2-7 , and its expression can be controlled by the BET-bromodomain (BRD4) inhibitor JQ1. lnc-HLX-2-7 is a candidate biomarker and a potential therapeutic target in group 3 medulloblastomas in children.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":130088,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":313913,"name":"Bongyong Lee","orcid":"0000-0003-3134-7093","position":1,"is_corresponding":false},{"id":582344,"name":"Haritha Kunhiraman","orcid":"0000-0002-1222-2650","position":2,"is_corresponding":false},{"id":274868,"name":"Cuncong Zhong","orcid":"0000-0002-8777-082X","position":3,"is_corresponding":false},{"id":582907,"name":"Rabi Murath","orcid":null,"position":4,"is_corresponding":false},{"id":582345,"name":"Jun Ying","orcid":"0009-0006-5684-794X","position":5,"is_corresponding":false},{"id":582346,"name":"Ben Liu","orcid":"0000-0001-8452-5397","position":6,"is_corresponding":false},{"id":249773,"name":"Alexandra Garancher","orcid":"0000-0001-5779-2860","position":7,"is_corresponding":false},{"id":582908,"name":"Ignacio González-Gómez","orcid":null,"position":8,"is_corresponding":false},{"id":558441,"name":"Hector Monforte","orcid":null,"position":9,"is_corresponding":false},{"id":582347,"name":"Stacie Stapleton","orcid":"0000-0001-6459-4360","position":10,"is_corresponding":false},{"id":132347,"name":"Rajeev Vibhakar","orcid":"0000-0002-5949-3896","position":11,"is_corresponding":false},{"id":24634,"name":"Chetan Bettegowda","orcid":"0000-0001-9991-7123","position":12,"is_corresponding":false},{"id":5559,"name":"Robert J. Wechsler‐Reya","orcid":"0000-0002-7463-8352","position":13,"is_corresponding":false},{"id":481526,"name":"George I. Jallo","orcid":"0000-0001-9607-6867","position":14,"is_corresponding":false},{"id":428976,"name":"Eric H. Raabe","orcid":"0000-0002-9368-7037","position":15,"is_corresponding":false},{"id":232275,"name":"Charles G. Eberhart","orcid":"0000-0002-2910-9427","position":16,"is_corresponding":false},{"id":313924,"name":"Ranjan J. Perera","orcid":"0000-0002-5926-3687","position":17,"is_corresponding":false},{"id":534993,"name":"Keisuke Katsushima","orcid":"0000-0001-7770-432X","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T23:15:53.196774Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}