MiR-920 and LSP1 co-regulate the growth and migration of glioblastoma cells by modulation of JAK2/STAT5 pathway
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MiR-920 and LSP1 co-regulate the growth and migration of glioblastoma cells by modulation of JAK2/STAT5 pathway Ping Cong 1 & Hua-Ying Hou 1 & Wei Wei 1 & Yong Zhou 1 & Xiao-Ming Yu 1 Received: 3 June 2020 / Accepted: 29 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract This study probes the function and mechanism of lymphocyte-specific protein 1 (LSP1) in glioblastoma pathogenesis. According to the data acquired from TCGA, Oncomine and GEO databases, the expression and prognostic value of LSP1 and miR-920 in glioblastoma patients were analyzed. The expression levels of LSP1 in U251 and A172 cell lines were analyzed by qRT-PCR and western blotting. CCK8, colony formation and transwell assays were utilized to test glioblastoma cell malignant abilities. Furthermore, the associations between LSP1 and miR-920 were indentified by bioinformatics analysis and rescue assays. Moreover, the protein expression levels of p-JAK2, JAK2, p-STAT5 and STAT5, as the hallmark of JAK/STAT5 signaling, were detected by western blotting. The observations showed that LSP1 was highly augmented in glioblastoma samples. Additionally, up-regulation of LSP1 was associated with a unfavorable prognosis in glioblastoma patients. Biological experiments revealed that depletion of LSP1 significantly suppressed the proliferation, invasion and migration of U251 and A172 cells. MiR-920, as an upstream regulator of LSP1, negatively modulated LSP1 expression and promoted U251 cells malignant behaviors after miR-920 inhibitor treatment. However, together knockdown LSP1 and miR-920 inhibited these effects. Moreover, the expression levels of p-JAK2 and p-STAT5 were increased or decreased in U251 cells after transfection of miR920 inhibitor or si-LPS1. Taken together, miR-920 might blocked the malignant development of glioblastoma cells, which is possibly realized by targeting LSP1 and modulation of JAK/STAT5 pathway. These findings implied that miR-920/LSP1 was a potential therapeutic target for glioblastoma treatment. Keywords Lymphocyte-specific protein 1 . Glioblastoma . Proliferation . Invasion . JAK2/STAT5 pathway
Introduction Glioblastoma, characterized by high morbidity and mortality, is the most frequent malignant brain tumor (Kim et al. 2019). Despite the utilization of many medical interventions, more than half of glioblastoma patients died within one year (Nie et al. 2019; Stupp et al. 2015). This lack of progress on glioblastoma treatment still exists in spite of good understandings of its biology (Hu et al. 2018). Therefore, finding underlying biological markers is meaningful for investigating novel therapeutic interventions for glioblastoma. Currently, more and more evidence has afforded the critical role of microRNAs (miRNAs) in malignant diseases, including glioblastoma
* Xiao-Ming Yu [email protected] 1
Department of Cancer Center, The Second Hospital of Shandong University, 247 Beiyuan Street, Jinan, Shandong 250033, People’s Republic of China
(Guo et al. 2019; Petrescu et al. 2019; Yan et a
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