The immune-related microRNA miR-146b is upregulated in glioblastoma recurrence

Shariq S. Khwaja, Chunyu Cai, Shahed N. Badiyan, Xiaowei Wang, Jiayi Huang

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Background: Glioblastoma (GBM) has a high rate of local recurrence despite chemoradiotherapy (CRT). Genome-wide expression profiling was performed on patient tumors before and after chemoradiotherapy to identify genes and gene pathways associated with recurrence. Results: Median time to recurrence was 8.9 months with median time to second surgery of 9.6 months. The microRNA (miRNA) analysis identified 9 oncologic and immune-related miRNAs to be differentially expressed, including the hypoxia-related miR-210 and the immune-modulatory miR-146b. More than 1200 differentiallyexpressed genes were identified with RNA-sequencing (RNA-seq). Gene set enrichment analysis (GSEA) identified p53 signaling, Notch, Wnt, VEGF, and MEK gene sets enriched in recurrent GBM. Consistent with the miRNA profiling data, the miR-146b target gene set from GSEA analysis was also associated with recurrence. Methods: Fourteen patients with GBM recurrence after CRT who had available tumor tissue from the initial diagnosis as well as recurrence were selected. Total RNA was isolated from formalin-fixed paraffin-embedded (FFPE) tumor specimens. Genome-wide expression profiling using RT-PCR for miRNA analysis and RNA-seq for messenger RNA (mRNA) analysis were conducted to identify differentially-expressed genes. GSEA was performed on the differential expression data. Conclusions: Genome-wide expression profiling identifies multiple oncologic and immune-related gene sets associated with GBM recurrence. In particular, immunerelated miR-146b is upregulated in recurrence and deserves further investigation.

Original languageEnglish (US)
Pages (from-to)29036-29046
Number of pages11
JournalOncotarget
Volume9
Issue number49
DOIs
Publication statusPublished - Jun 26 2018

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Keywords

  • GBM
  • Gene expression profiling
  • Glioma
  • MiR-146b
  • Recurrence

ASJC Scopus subject areas

  • Oncology

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