Open Access

Regulation of gliomagenesis and stemness through acid sensor ASIC1a

  • Authors:
    • Pendelton King
    • Jingwei Wan
    • Alyssa Aihui Guo
    • Shanchun Guo
    • Yugang Jiang
    • Mingli Liu
  • View Affiliations

  • Published online on: September 10, 2021     https://doi.org/10.3892/ijo.2021.5262
  • Article Number: 82
  • Copyright: © King et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glioblastoma multiforme (GBM) is the most prevalent and aggressive type of adult gliomas. Despite intensive therapy including surgery, radiation, and chemotherapy, invariable tumor recurrence occurs, which suggests that glioblastoma stem cells (GSCs) render these tumors persistent. Recently, the induction of GSC differentiation has emerged as an alternative method to treat GBM, and most of the current studies aim to convert GSCs to neurons by a combination of transcriptional factors. As the tumor microenvironment is typically acidic due to increased glycolysis and consequently leads to an increased production of lactic acid in tumor cells, in the present study, the role of acid‑sensing ion channel 1a (ASIC1a), an acid sensor, was explored as a tumor suppressor in gliomagenesis and stemness. The bioinformatics data from The Cancer Genome Atlas revealed that ASIC1 expression levels in GBM tumor tissues were lower than those in normal brain, and glioma patients with high ASIC1 expression had longer survival than those with low ASIC1 expression. Our immunohistochemistry data from tissue microarray revealed that ASIC1a expression was negatively associated with glioma grading. Functional studies revealed that the downregulation of ASIC1a promoted glioma cell proliferation and invasion, while upregulation of ASIC1a inhibited their proliferation and invasion. Furthermore, ASIC1a suppressed growth and proliferation of glioma cells through G1/S arrest and apoptosis induction. Mechanistically, ASIC1a negatively modulated glioma stemness via inhibition of the Notch signaling pathway and GSC markers CD133 and aldehyde dehydrogenase 1. ASIC1a is a tumor suppressor in gliomagenesis and stemness and may serve as a promising prognostic biomarker and target for GBM patients.

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October-2021
Volume 59 Issue 4

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

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Spandidos Publications style
King P, Wan J, Guo AA, Guo S, Jiang Y and Liu M: Regulation of gliomagenesis and stemness through acid sensor ASIC1a. Int J Oncol 59: 82, 2021
APA
King, P., Wan, J., Guo, A.A., Guo, S., Jiang, Y., & Liu, M. (2021). Regulation of gliomagenesis and stemness through acid sensor ASIC1a. International Journal of Oncology, 59, 82. https://doi.org/10.3892/ijo.2021.5262
MLA
King, P., Wan, J., Guo, A. A., Guo, S., Jiang, Y., Liu, M."Regulation of gliomagenesis and stemness through acid sensor ASIC1a". International Journal of Oncology 59.4 (2021): 82.
Chicago
King, P., Wan, J., Guo, A. A., Guo, S., Jiang, Y., Liu, M."Regulation of gliomagenesis and stemness through acid sensor ASIC1a". International Journal of Oncology 59, no. 4 (2021): 82. https://doi.org/10.3892/ijo.2021.5262