MiR-920 and LSP1 co-regulate the growth and migration of glioblastoma cells by modulation of JAK2/STAT5 pathway
Autor: | Huaying Hou, Ping Cong, Yong Zhou, Wei Wei, Xiaoming Yu |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Physiology Regulator Lymphocyte-Specific Protein 1 Cell Growth Processes Transfection Pathogenesis 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor STAT5 Transcription Factor Humans STAT5 Gene knockdown biology Brain Neoplasms Tumor Suppressor Proteins Microfilament Proteins Cell Biology Janus Kinase 2 Blot MicroRNAs 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Cancer research biology.protein Glioblastoma Signal Transduction |
Zdroj: | Journal of bioenergetics and biomembranes. 52(5) |
ISSN: | 1573-6881 |
Popis: | 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 miR-920 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. |
Databáze: | OpenAIRE |
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