SKA1 promotes malignant phenotype and progression of glioma via multiple signaling pathways

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.

Identification of HCG18 and MCM3AP-AS1 That Associate With Bone Metastasis, Poor Prognosis and Increased Abundance of M2 Macrophage Infiltration in Prostate Cancer

“…40 Knockdown of SKA1 repressed the ability of cell proliferation, migration and invasion of PCa 41 and glioma. 40 SKA2 expression was also increased in breast cancer tissues and cells, and associated with lymph node metastasis. SKA2 knockdown significantly reduced the migration and invasion by reversing EMT.…”

Identification of Spindle and Kinetochore-Associated Family Genes as Therapeutic Targets and Prognostic Biomarkers in Pancreas Ductal Adenocarcinoma Microenvironment

“…Multiple studies have reported that SKA1 promotes cancer progression in a variety of tumors (13,19,(57)(58)(59)(60)(61). An in vitro study found that SKA1 accelerates cell proliferation and cancer progression in glioma via tumor-associated signaling pathways, including cell cycle and Wnt/β-catenin signaling (62). An immunohistochemical study of 126 hepatocellular carcinoma patients revealed that SKA1 expression is significantly elevated in tumor tissues, and it can regulate the hepatocellular carcinoma cell cycle and contributes to poor prognosis (63).…”

Circular RNA FAT atypical cadherin 1 (circFAT1)/microRNA-525-5p/spindle and kinetochore-associated complex subunit 1 (SKA1) axis regulates oxaliplatin resistance in breast cancer by activating the notch and Wnt signaling pathway

“…SKA1 has been proven to accelerate tumorigenesis through the activation of several signaling pathways [ 22 ]. Herein, Gene Set Enrichment Analysis (GSEA) indicated that Notch and Wnt signaling pathways were both positively associated with SKA1 expression in BC ( Figure 6a ).…”