# Regulation, function, and the therapeutic potential of an oncogenic long noncoding RNA lnc-HLX-2-7 in group 3 medulloblastomas

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $417,621

## Abstract

Project Summary
Brain tumors are relatively common in children, with medulloblastoma (MB) the most frequent
type, especially in children under five. MBs can spread through the cerebrospinal fluid, and
metastases are common at the time of diagnosis. Some of the regulatory genes, signaling
pathways, and gene regulatory networks in MB are known, but the role of non-coding RNAs in
MB, particularly long non-coding RNAs (lncRNAs), are poorly described. By applying machine
learning to publicly available RNA-seq datasets, we found that lnc-HLX2-7 was highly upregulated
and specific for difficult-to-treat and poor prognosis grade 3 (G3) MBs compared with other
molecular subgroups. CRISPR-Cas9 depletion of lnc-HLX-2-7 in G3 MB cells significantly
reduced cell proliferation, invasion, and 3D colony formation and induced apoptosis. When lnc-
HLX-2-7-deleted G3 MB cells were injected into the mouse cerebellum, they produced
considerably smaller tumors than those derived from parental cells. Further, cerium oxide
nanoparticle-coated antisense oligonucleotides (ASOs) against lnc-HLX2-7 reduced in vivo tumor
growth. Our preliminary results also demonstrate that lnc-HLX-2-7 is a critical MB metabolic
regulator that modulates NAD+ (nicotinamide adenine dinucleotide) via nicotinamide
phosphoribosyltransferase (NAMPT), a key enzyme mediating NAD+ production. The above
results highlight the functional impact of lnc-HLX-2-7 on G3 MB development, some of the
underlying mechanisms of action, and its importance as a therapeutic target. Our central
hypothesis is that lnc-HLX-2-7 is an important oncogenic molecule that can be therapeutically
targeted in G3 MBs. We propose the following three Specific Aims to test our hypothesis: (a) to
test pre-clinical therapeutics targeting G3 MBs; (b) to delineate the lnc-HLX-2-7-driven molecular
mechanisms underlying G3 MB tumors, and (c) to identify how lnc-HLX-2-7 is regulated and
regulates other genes in G3 MBs. This study will provide valuable mechanistic insights into how
lnc-HLX-2-7 drives G3 MB development, advance pre-clinical therapeutic targeting of this
challenging subgroup, and anticipate compensatory and resistance mechanisms. This study
provides important insights into how lncRNAs function as critical oncogenes in the brain and other
cancers.

## Key facts

- **NIH application ID:** 10518721
- **Project number:** 1R01NS124668-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Ranjan Joseph Perera
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $417,621
- **Award type:** 1
- **Project period:** 2022-07-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10518721

## Citation

> US National Institutes of Health, RePORTER application 10518721, Regulation, function, and the therapeutic potential of an oncogenic long noncoding RNA lnc-HLX-2-7 in group 3 medulloblastomas (1R01NS124668-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10518721. Licensed CC0.

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