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

  • Authors:
    • Narae Jung
    • Ho Jeong Kwon
    • Hye Jin Jung
  • View Affiliations

  • Published online on: November 6, 2017     https://doi.org/10.3892/ijo.2017.4191
  • Pages:241-251
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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.

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January 2018
Volume 52 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
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APA
Jung, N., Kwon, H.J., & Jung, H.J. (2018). Downregulation of mitochondrial UQCRB inhibits cancer stem cell-like properties in glioblastoma. International Journal of Oncology, 52, 241-251. https://doi.org/10.3892/ijo.2017.4191
MLA
Jung, N., Kwon, H. J., Jung, H. J."Downregulation of mitochondrial UQCRB inhibits cancer stem cell-like properties in glioblastoma". International Journal of Oncology 52.1 (2018): 241-251.
Chicago
Jung, N., Kwon, H. J., Jung, H. J."Downregulation of mitochondrial UQCRB inhibits cancer stem cell-like properties in glioblastoma". International Journal of Oncology 52, no. 1 (2018): 241-251. https://doi.org/10.3892/ijo.2017.4191