Related Experiment Video
Updated: Jul 1, 2025

Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells
Published on: September 1, 2010
A therapeutically targetable positive feedback loop between lnc-HLX-2-7, HLX, and MYC that promotes group 3
Keisuke Katsushima1, Kandarp Joshi1, Menglang Yuan1
1Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, 1650 Orleans St., Baltimore, MD 21231, USA; Johns Hopkins All Children's Hospital, 600 5th St. South, St. Petersburg, FL 33701, USA.
Abstract:
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 in the promoter region of HLX, a sense-overlapping gene of lnc-HLX-2-7, which activates HLX expression by recruiting multiple factors, including enhancer elements. RNA sequencing and chromatin immunoprecipitation reveal that HLX binds to and activates the promoters of several oncogenes, including TBX2, LIN9, HOXM1, and MYC. Intravenous treatment with cerium-oxide-nanoparticle-coated antisense oligonucleotides targeting lnc-HLX-2-7 (CNP-lnc-HLX-2-7) inhibits tumor growth by 40%-50% in an intracranial MB xenograft mouse model. Combining CNP-lnc-HLX-2-7 with standard-of-care cisplatin further inhibits tumor growth and significantly prolongs mouse survival compared with CNP-lnc-HLX-2-7 monotherapy. Thus, the lnc-HLX-2-7-HLX-MYC axis is important for regulating G3 MB progression, providing a strong rationale for using lnc-HLX-2-7 as a therapeutic target for G3 MBs.
Insights
A newly identified long non-coding RNA, lnc-HLX-2-7, drives group 3 medulloblastoma (G3 MB) progression. Targeting this RNA with nanoparticles significantly inhibits tumor growth and enhances survival.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development.
- Group 3 medulloblastoma (G3 MB) is an aggressive pediatric brain tumor with limited therapeutic options.
Purpose of the Study:
- To investigate the role of lnc-HLX-2-7 in G3 MB pathogenesis.
- To evaluate lnc-HLX-2-7 as a potential therapeutic target for G3 MB.
Main Methods:
- RNA sequencing and chromatin immunoprecipitation were used to identify and characterize the lnc-HLX-2-7 regulatory pathway.
- In vivo studies utilized an intracranial G3 MB xenograft mouse model treated with cerium-oxide-nanoparticle-coated antisense oligonucleotides (CNP-lnc-HLX-2-7).
Main Results:
- lnc-HLX-2-7 was found to activate the oncogene HLX by recruiting enhancer elements.
- HLX was shown to activate key oncogenes including MYC, LIN9, TBX2, and HOXM1.
- CNP-lnc-HLX-2-7 treatment reduced tumor growth by 40%-50% in a mouse model.
- Combination therapy with CNP-lnc-HLX-2-7 and cisplatin significantly improved survival.
Conclusions:
- The lnc-HLX-2-7-HLX-MYC axis is a critical regulator of G3 MB progression.
- lnc-HLX-2-7 represents a promising therapeutic target for G3 MB.
Related Concept Videos
Abnormal Proliferation
Hedgehog Signaling Pathway
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Targeted Cancer Therapies
There are several types of targeted therapies against...

