Abstract
BackgroundSpindle and kinetochore associated protein 1 (SKA1) is a protein involved in chromosome congression and mitosis. It has been found to be upregulated and oncogenic in several human cancers. Herein, we investigated the precise role of SKA1 in the progression and malignant phenotype of human glioma.MethodsBioinformatic analysis was carried out based on the RNA-seq data and corresponding clinical data from GEO, TCGA and CGGA databases. Western blot was performed to analyze the expression of SKA1 in clinical samples and signaling pathway proteins in glioma cells, respectively. CCK8 assay, colony forming assay and EdU assay were performed to assess the cell viability. Cell migration and invasion assays were also performed. Moreover, xenograft model was established and the expression of SKA1 was assessed in the xenograft by immunohistochemistry.ResultsSKA1 expression is positively correlated with glioma grade and could be a promising biomarker for GBM. Moreover, overexpression of SKA1 may lead to poor prognosis in glioma. Downregulation of SKA1 attenuated cell viability, migration, and invasion in U251, U87, LN229 and T98 cells. Furthermore, GSEA analysis demonstrated that SKA1 was involved in the cell cycle, EMT pathway as well as Wnt/β-catenin signaling pathway, which were then confirmed with Western blot analysis.ConclusionSKA1 promotes malignant phenotype and progression of glioma via multiple pathways, including cell cycle, EMT, Wnt/β-catenin signaling pathway. Therefore, SKA1 could be a promising therapeutic target for the treatment of human gliomas.
Highlights
Spindle and kinetochore associated protein 1 (SKA1) is a protein involved in chromosome congression and mitosis
SKA1 expression was positively associated with glioma grade First, SKA1 expression was determined in public data deposited in TCGA database and GEO dataset (GSE 4290)
We found that SKA1 expression was markedly increased in high grade glioma (Grade IV and III), but there was no significant difference between low grade glioma (Grade II) and non-tumor brain tissues (Fig. 1a)
Summary
Spindle and kinetochore associated protein 1 (SKA1) is a protein involved in chromosome congression and mitosis. We investigated the precise role of SKA1 in the progression and malignant phenotype of human glioma. Glioblastoma is the most malignant type of glioma and leads to poor survival despite of aggressive therapy including surgery, radiotherapy and chemotherapy [2,3,4,5]. The 2016 WHO classification of tumors of the central nervous system proposed the priority of integrated histological and molecular classification system in brain tumor diagnosis, which enables more precise patient stratification [1]. Spindle and kinetochore associated complex (SKA complex) is required for timely anaphase onset. This family is composed of three proteins: SKA1, SKA2 and SKA3, which facilitates the processive movement of
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