Open AccessGelsolin inhibits malignant phenotype of glioblastoma and is regulated by miR‐654‐5p and miR‐450b‐5p
Author(s) -
Zhang Jiakang,
Furuta Takuya,
Sabit Hemragul,
Tamai Sho,
Jiapaer Shabierjiang,
Dong Yu,
Kinoshita Masashi,
Uchida Yasuo,
Ohtsuki Sumio,
Terasaki Tetsuya,
Zhao Shiguang,
Nakada Mitsutoshi
Publication year - 2020
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14429
Subject(s) - gelsolin , gene knockdown , western blot , cancer research , biology , microrna , cell growth , immunohistochemistry , small hairpin rna , phenotype , in vivo , microbiology and biotechnology , cell culture , immunology , actin , gene , biochemistry , genetics
Abstract We have previously shown that gelsolin (GSN) levels are significantly lower in the blood of patients with glioblastoma (GBM) than in healthy controls. Here, we analyzed the function of GSN in GBM and examined its clinical significance. Furthermore, microRNAs involved in GSN expression were also identified. The expression of GSN was determined using western blot analysis and found to be significantly lower in GBM samples than normal ones. Gelsolin was mainly localized in normal astrocytes, shown using immunohistochemistry and immunofluorescence. Higher expression of GSN was correlated with more prolonged progression‐free survival and overall survival. Gelsolin knockdown using siRNA and shRNA markedly accelerated cell proliferation and invasion in GBM in vitro and in vivo. The inactive form of glycogen synthase kinase‐3β was dephosphorylated by GSN knockdown. In GBM tissues, the expression of GSN and microRNA (miR)‐654‐5p and miR‐450b‐5p showed an inverse correlation. The miR‐654‐5p and miR‐450b‐5p inhibitors enhanced GSN expression, resulting in reduced proliferation and invasion. In conclusion, GSN, which inhibits cell proliferation and invasion, is suppressed by miR‐654‐5p and miR‐450b‐5p in GBM, suggesting that these miRNAs can be targets for treating GBM.