Allopregnanolone suppresses glioblastoma survival through decreasing DPYSL3 and S100A11 expression

Yin Hsun Feng, Sher Wei Lim, Hong Yi Lin, Shao An Wang, Sung Po Hsu, Tzu Jen Kao, Chiung Yuan Ko, Tsung I. Hsu

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

Allopregnanolone (allo) is a physiological regulator of neuronal activity that treats multiple neurological disorders. Allo penetrates the blood–brain barrier with very high efficiency, implying that allo can treat CNS-related diseases, including glioblastoma (GBM), which always recurs after standard therapy. Hence, this study aimed to determine whether allo has a therapeutic effect on GBM. We found that allo enhanced temozolomide (TMZ)-suppressed cell survival and proliferation of TMZ-resistant cells. In particular, allo enhanced TMZ-inhibited cell migration and TMZ-induced apoptosis. Additionally, allo strongly induced DNA damage characterized by γH2Ax. Furthermore, quantitative proteomic analysis, iTRAQ, showed that allo significantly decreased the levels of DPYSL3, S100A11, and S100A4, reflecting the poor prognosis of patients with GBM confirmed by differential gene expression and survival analysis. Moreover, single-cell RNA-Seq revealed that S100A11, expressed in malignant cells, oligodendrocytes, and macrophages, was significantly associated with immune cell infiltration. Furthermore, overexpression of DPYSL3 or S100A11 prevented allo-induced cell death. In conclusion, allo suppresses GBM cell survival by decreasing DPYSL3/S100A11 expression and inducing DNA damage.

原文英語
文章編號106067
頁(從 - 到)106067
期刊Journal of Steroid Biochemistry and Molecular Biology
219
DOIs
出版狀態已發佈 - 5月 2022

ASJC Scopus subject areas

  • 內分泌學、糖尿病和代謝
  • 生物化學
  • 分子醫學
  • 分子生物學
  • 內分泌
  • 臨床生物化學
  • 細胞生物學

指紋

深入研究「Allopregnanolone suppresses glioblastoma survival through decreasing DPYSL3 and S100A11 expression」主題。共同形成了獨特的指紋。

引用此