Downregulation of mitochondrial UQCRB inhibits cancer stem cell-like properties in glioblastoma

Narae Jung, Ho Jeong Kwon, Hye Jin Jung

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Glioblastoma stem cell targeted therapies have become a powerful strategy for the treatment of this deadliest brain tumor. We demonstrate for the first time that downregulation of mitochondrial ubiquinol-cytochrome c reductase binding protein (UQCRB) inhibits the cancer stem cell-like properties in human glioblastoma cells. The synthetic small molecules targeting UQCRB significantly suppressed not only the self-renewal capacity such as growth and neurosphere formation, but also the metastatic potential such as migration and invasion of glioblastoma stem-like cells (GSCs) derived from U87MG and U373MG at subtoxic concentrations. Notably, the UQCRB inhibitors repressed c-Met-mediated downstream signal transduction and hypoxia-inducible factor-1α (HIF-1α) activation, thereby reducing the expression levels of GSC markers including CD133, Nanog, Oct4 and Sox2 in the GSCs. Furthermore, the UQCRB inhibitors decreased mitochondrial ROS generation and mitochondrial membrane potential in the GSCs, indicating that they regulate the mitochondrial function in GSCs. Indeed, the knockdown of UQCRB gene by UQCRB siRNA significantly inhibited the cancer stem cell-like phenotypes as well as the expression of stemness markers by blocking mitochondrial ROS/HIF-1α/ c-Met pathway in U87MG GSCs. These findings suggest that UQCRB and its inhibitors could be a new therapeutic target and lead compounds for eliminating cancer stem cells in glioblastoma.

Original languageEnglish
Pages (from-to)241-251
Number of pages11
JournalInternational journal of oncology
Volume52
Issue number1
DOIs
Publication statusPublished - 2018 Jan

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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