Gelsolin inhibits malignant phenotype of glioblastoma and is regulated by miR‐654‐5p and miR‐450b‐5p. Issue 7 (29th May 2020)

• Record Type: Journal Article
• Authors: Zhang, Jiakang; Furuta, Takuya; Sabit, Hemragul; Tamai, Sho; Jiapaer, Shabierjiang; Dong, Yu; Kinoshita, Masashi; Uchida, Yasuo; Ohtsuki, Sumio; Terasaki, Tetsuya; Zhao, Shiguang; Nakada, Mitsutoshi
• Is Part Of: Cancer science. Volume 111:Issue 7(2020)
• Page Start: 2413
• Page End: 2422
• Publication Date: 2020-05-29
• Subjects: gelsolin -- glioblastoma -- GSK3β -- miR‐450b‐5p -- miR‐654‐5p; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14429
• Languages: English
• ISSNs: 1347-9032

Abstract

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. Abstract : Downregulation of gelsolin (GSN) contributed to the short survival of glioblastoma. GSN suppressed proliferation and invasion in glioma cells, possibly through the phosphorylation of glycogen synthase kinase (GSK)‐3βSer9, which is the inactive form of GSK3β. GSN was downregulated by microRNA (miR)‐654‐5p and miR‐450b‐5p in glioblastoma, suggesting that these miRs might be good targets for glioblastoma treatment.