Targeting Novel Long Non-Coding RNA May Improve Glioblastoma Treatment - News Center Targeting Novel Long Non-Coding RNA May Improve Glioblastoma Treatment Scientific Advances Targeting Novel Long Non-Coding RNA May Improve Glioblastoma Treatment By Melissa Rohman Apr 13, 2026 Shi-Yuan Cheng, PhD, professor in the Ken and Ruth Davee Department of Neurology’s Division of Neuro-oncology, was a co-corresponding author of the study published in Nature Cell Biology. Scientists have discovered that increased expression of a novel long non-coding RNA drives glioblastoma cell growth alongside a genetic amplification found in more than half of glioblastoma tumors, according to a Northwestern Medicine study published in Nature Cell Biology. The findings may inform new therapeutic strategies that improve treatment sensitivity and response in glioblastoma, said Shi-Yuan Cheng, PhD, professor in the Ken and Ruth Davee Department of Neurology ’s Division of Neuro-oncology and a co-corresponding author of the study. “We have another way to target this tumor resistance. We identified two separate targets that we can then target with enhanced EGFR inhibitor therapy,” said Cheng, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Glioblastoma is the most common and aggressive primary brain tumor in adults, according to the National Brain Tumor Society, and the five-year survival rate has remained less than 7 percent. More than half of glioblastoma tumors have EGFR amplification. EGFR is commonly amplified in extrachromosomal DNAs — double-stranded circular DNAs that are known to drive oncogene amplification and dysregulated gene expression in tumor cells. However, therapeutic strategies have yet to successfully target EGFR in glioblastoma. In the study, the scientists used RNA sequencing techniques to study the involvement of long non-coding RNAs (lncRNAs) — RNA transcripts containing more than 200 nucleotides — in EGFR -amplified glioblastoma cell lines and discovered a previously unknown lncRNA that is co-amplified alongside EGFR , which they named “hidden EGFR long non-coding downstream RNA,” or HELDR Additionally, they discovered that HELDR exhibits widespread genomic DNA binding: HELDR binds to promoters, gene bodies and intergenic regions to regulate global gene expression without affecting EGFR signaling. Xiaozhou Yu, PhD, a postdoctoral fellow in the Cheng laboratory and lead author of the study. Next, using a chromatin isolation by RNA purification (ChIRP) technique to map the chromosome binding sites of HELDR, the scientists found that HELDR recruits the transcription co-activator p300 to the promoter of the histone-modifying enzyme KAT7. This results in increased levels of epigenetic modification, the recruitment of transcription factors and enhanced transcription of KAT7. “We had highly enriched DNA and could map binding sites across the whole genome, which was a novel part of our study,” said Xiaozhou Yu, PhD, a postdoctoral fellow in the Cheng laboratory and lead author of the study. Lastly, the investigators found that this HELDR–KAT7 axis supports the expression of genes associated with glioblastoma resistance to EGFR inhibitors (EGFRis). In patient-derived glioblastoma cell lines, they found that therapeutically targeting KAT7 or HELDR enhanced treatment response to EGFRis in vivo The findings that targeting epigenetic programs driven by HELDR may increase treatment sensitivity of EGFR inhibitors in glioblastoma, according to the authors. Bo Hu, PhD , professor of Neurology in the Division of Neuro-oncology, was a co-corresponding author of the study. Co-authors of the study include Xiao Song, PhD , research assistant professor of Neurology in the Division of Neuro-oncology; Qingshu Meng, PhD , research assistant professor of Urology; Maya Walker, a student in the Driskill Graduate Program in Life Sciences ( DGP ); Qi Cao, PhD , the Anthony J. Schaeffer, MD, Professor of Urology; and Rendong Yang, PhD , associate professor of Urology. Cao and Yang are also members of the Lurie Cancer Center. This work was supported by National Institute of Health (NIH) grants NS113160, NS126810, NS115403, NS122375, NS125318, CA234799, CA259388, GM142441, CA285684, CA278832, CA256741 and P50CA180995 Development Research Program; United States Army Medical Research Acquisition Activity grants W81XWH-22-10373, W81XWH-22-1-0374 and HT9425-24-1-0573; and the Polsky Urologic Cancer Institute of the Robert H. Lurie Comprehensive Cancer Center of NU at Northwestern Memorial Hospital. Cancer Neurology Research Latest News Visionary Biochemist Delivers 2026 Kimberly Prize Lecture Apr 23, 2026 Bass Named 2026 AAAS Member Apr 22, 2026 Neighborhood Social Factors Increase Cardiovascular Disease Risk Apr 21, 2026 Little-Used Cholesterol Test Could Prevent More Heart Attacks, Strokes Apr 20, 2026 Cells ‘Switch’ on Protein Factories After Injury, Study Finds Apr 17, 2026 Epilepsy Gene Implicated in Severe Migraine Disorder Apr 16, 2026