A Novel C19orf47-AKT2 Chimeric RNA Generated by Cis-Splicing of Adjacent Genes Is Associated With Glioblastoma

Zihan Wang1,2, Bowen Ni3, Kezhi Wu3

  • 1Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.

Abstract

Insights

Novel chimeric RNAs, C19orf47-AKT2, were found in gliomas and promote tumor growth. These findings suggest C19orf47-AKT2 chimeras could be new biomarkers and therapeutic targets for glioma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Malignant gliomas present significant challenges in treatment.
  • Novel molecular targets are crucial for advancing precision oncology.

Purpose of the Study:

  • To identify and characterize novel chimeric RNAs in glioma.
  • To assess the clinical and functional significance of these chimeras for targeted glioma therapy.

Main Methods:

  • RNA sequencing and polymerase chain reaction (PCR) were used to identify and validate C19orf47-AKT2 chimeric RNAs.
  • Quantitative PCR and Kaplan-Meier analysis assessed expression and prognostic significance in glioblastoma.
  • Genomic analysis, Western blotting, and CCK-8 assays investigated formation mechanisms and functional impact on glioma proliferation.

Main Results:

  • C19orf47-AKT2 chimeric RNAs were detected in 88.9% of glioma core tissues, significantly more than in peritumoral tissues.
  • High expression of the C19orf47e9-AKT2e2 variant correlated with poor glioblastoma prognosis.
  • Downregulation of these chimeras suppressed patient-derived glioblastoma cell proliferation, despite no detected endogenous fusion protein.

Conclusions:

  • Novel C19orf47-AKT2 chimeras, formed via cis-splicing, may function as noncoding RNAs promoting glioblastoma proliferation.
  • These chimeras represent potential prognostic markers and therapeutic targets for glioma treatment.

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