TY - JOUR
T1 - Allopregnanolone suppresses glioblastoma survival through decreasing DPYSL3 and S100A11 expression
AU - Feng, Yin Hsun
AU - Lim, Sher Wei
AU - Lin, Hong Yi
AU - Wang, Shao An
AU - Hsu, Sung Po
AU - Kao, Tzu Jen
AU - Ko, Chiung Yuan
AU - Hsu, Tsung I.
N1 - Funding Information:
We are grateful for the support of the TMU Research Center of Cancer Translational Medicine from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan.
Funding Information:
This work was supported by grants 107CM-TMU-13 and 109CM-TMU-15 from Chi Mei Hospital-TMU joint research project and the Ministry of Science and Technology of Taiwan ( MOST 108-2628-B-038-005 , 109-2628-B-038-017- and 110-2628-B-038-021- ).
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
KW - Allopregnanolone
KW - Glioblastoma
KW - iTRAQ
UR - http://www.scopus.com/inward/record.url?scp=85124312111&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85124312111&partnerID=8YFLogxK
U2 - 10.1016/j.jsbmb.2022.106067
DO - 10.1016/j.jsbmb.2022.106067
M3 - Article
C2 - 35114375
AN - SCOPUS:85124312111
SN - 0960-0760
VL - 219
SP - 106067
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
M1 - 106067
ER -
