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Single-cell RNA-seq reveals RAD51AP1 as a potent mediator of EGFRvIII in human glioblastomas

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机构: [1]Tianjin Med Univ, Gen Hosp, Tianjin, Peoples R China [2]Minist Educ & Tianjin Municipal Govt, Key Lab Neurotrauma Variat & Regenerat, Tianjin Neurol Inst, Tianjin 300052, Peoples R China [3]Hebei Univ, Med Coll, Dept Pathol, Baoding 071000, Hebei, Peoples R China [4]Hebei Univ,Affiliated Hosp,Dept Neurosurg,Baoding 071000,Peoples R China [5]Nankai Univ, Tianjin Huanhu Hosp, Dept Neurosurg, Radiosurg Ctr, Tianjin 300350, Peoples R China [6]Capital Med Univ, Beijing Neurosurg Inst, Beijing 100050, Peoples R China [7]Guangzhou Med Univ, Affiliated Canc Hosp & Inst, Guangzhou 510095, Guangdong, Peoples R China
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关键词: glioblastoma heterogenous EGFRvIII single-cell sequencing RAD51AP1

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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.

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出版当年[2020]版:
大类 | 2 区 医学
小类 | 1 区 老年医学 3 区 细胞生物学
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出版当年[2019]版:
Q1 GERIATRICS & GERONTOLOGY Q2 CELL BIOLOGY
最新[2023]版:
Q2 CELL BIOLOGY Q2 GERIATRICS & GERONTOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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第一作者机构: [1]Tianjin Med Univ, Gen Hosp, Tianjin, Peoples R China [2]Minist Educ & Tianjin Municipal Govt, Key Lab Neurotrauma Variat & Regenerat, Tianjin Neurol Inst, Tianjin 300052, Peoples R China
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通讯机构: [1]Tianjin Med Univ, Gen Hosp, Tianjin, Peoples R China [2]Minist Educ & Tianjin Municipal Govt, Key Lab Neurotrauma Variat & Regenerat, Tianjin Neurol Inst, Tianjin 300052, Peoples R China [7]Guangzhou Med Univ, Affiliated Canc Hosp & Inst, Guangzhou 510095, Guangdong, Peoples R China
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