Research Paper Volume 11, Issue 18 pp 7707—7722
Single-cell RNA-seq reveals RAD51AP1 as a potent mediator of EGFRvIII in human glioblastomas
- 1 Tianjin Medical University General Hospital, Tianjin 300052, China
- 2 Tianjin Neurological Institute, Key Laboratory of Neurotrauma, Variation, and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin 300052, China
- 3 Department of Pathology, Medical College of Hebei University, Baoding, Hebei 071000, China
- 4 Department of Neurosurgery, Hebei University Affiliated Hospital, Baoding 071000, China
- 5 Radiosurgery Center, Department of Neurosurgery, Tianjin Huanhu Hospital, Nankai University, Tianjin 300350, China
- 6 Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China
- 7 Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, China
Received: August 4, 2019 Accepted: September 5, 2019 Published: September 18, 2019
https://doi.org/10.18632/aging.102282How to Cite
Copyright © 2019 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Recent advances in single-cell RNA sequencing (scRNA-seq) have endowed researchers with the ability to detect and analyze the transcriptomes of individual cancer cells. In the present study, 16,128 tumor cells from EGFR wild-type and EGFRvIII mutant cells were profiled by scRNA-seq. Analyses of scRNA-seq data from both U87MG and U87MG-EGFRvIII libraries revealed inherent heterogeneity in gene expression and biological processes. The cells stably expressing EGFRvIII showed enhanced transcriptional activities and a relatively homogeneous pattern, which manifested as less diverse distributions, gene expression levels and functional annotations compared with those of cells expressing the nonmutated version. Moreover, the differentially expressed genes between the U87MG and U87MG-EGFRvIII groups were mainly enriched in DNA replication, DNA repair and angiogenesis. We compared scRNA-seq data with bulk RNA-seq and EGFRvIII xenograft RNA-seq data. RAD51AP1 was shown to be upregulated in all three databases. Further analysis of RAD51AP1 revealed that it is an independent prognostic factor of glioma. Knocking down RAD51AP1 significantly inhibited tumor volume in an intracranial EGFRvIII-positive GBM model and prolonged survival time. Collectively, our microfluidic-based scRNA-seq driven by a single genetic event revealed a previously unappreciated implication of EGFRvIII in the heterogeneity of GBM and identified RAD51AP1 as an oncogene in glioma.