SKA3 promotes cell proliferation and migration in cervical cancer by activating the PI3K/Akt signaling pathway

Abstract

BackgroundCervical cancer (CC) is one of the most common cancers among females worldwide. Spindle and kinetochore-associated complex subunit 3 (SKA3), located on chromosome 13q, was identified as a novel gene involved in promoting malignant transformation in cancers. However, the function and underlying mechanisms of SKA3 in CC remain unknown. Using the Oncomine database, we found that expression of SKA3 mRNA is higher in CC tissues than in normal tissues and is linked with poor prognosis.MethodsIn our study, immunohistochemistry showed increased expression of SKA3 in CC tissues. The effect of SKA3 on cell proliferation and migration was evaluated by CCK8, clone formation, Transwell and wound-healing assays in HeLa and SiHa cells with stable SKA3 overexpression and knockdown. In addition, we established a xenograft tumor model in vivo.ResultsSKA3 overexpression promoted cell proliferation and migration and accelerated tumor growth. We further identified that SKA3 is involved in regulating cell cycle progression and the PI3K/Akt signaling pathway via RNA-sequencing (RNA-Seq) and gene set enrichment analyses. Western blotting results revealed that SKA3 overexpression increased levels of p-Akt, cyclin E2, CDK2, cyclin D1, CDK4, E2F1 and p-Rb in HeLa cells. Additionally, the use of an Akt inhibitor (GSK690693) significantly reversed the cell proliferation capacity induced by SKA3 overexpression in HeLa cells.ConclusionsWe suggest that SKA3 overexpression contributes to CC cell growth and migration by promoting cell cycle progression and activating the PI3K–Akt signaling pathway, which may provide potential novel therapeutic targets for CC treatment.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0670-4) contains supplementary material, which is available to authorized users.

SKA3 promotes lung adenocarcinoma metastasis through the EGFR–PI3K–Akt axis

“…Co-Ips indicated an interaction between SKA3 and EGFR, which influenced EGFR phosphorylation and activation. Similar to the present study, recent findings indicated that SKA3 promotes cell proliferation and migration in cervical cancer tissue through its ability to activate PI3K/Akt signaling [11]. However, we found that SKA3 interacts with EGFR to enhance PI3K-AKT activity, which was a novel finding.…”

“…SKA3 mutations are common in breast cancer, and were regulated cell growth [10]. Studies have shown that SKA3 mediates the metastatic profile and outcome of several cancers [11,12]. Using the GEPIA database to analyze LUAD tissue, SKA3 mRNA expression was elevated and correlated to poor survival outcomes in LUAD patients.…”

Identification of 13 Key Genes Correlated With Progression and Prognosis in Hepatocellular Carcinoma by Weighted Gene Co-expression Network Analysis

“…On the basis of gene enrichment analysis (GSEA), SKA3 was enriched in the cell cycle and P53 signaling pathways and these results were verified (Hou et al, 2019). Moreover, it has been reported that SKA3 can facilitate PI3K/AKT signaling pathway to promote cell cycle and progression in cervical cancer (Hu et al, 2018).…”

Combination of Berberine and Matrine Affects Apoptosis and Cellcycle in Human Cervical Cancer Cells

“…After the cells had attached, the medium in all wells was replaced with fresh culture medium for the controls or medium containing the respective compound concentrations. Four replicates of each concentration were tested to investigate the effect of berberine (3, 10, 30, 100, and 300 µmol/L) and matrine (1,3,10,30, and 100 mmol/L) against HeLa and SiHa cells. After incubating for 24 h, 20 µL of 5 mg/mL 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution was added to each well, followed by incubation for 4 h in the incubator, after which the supernatant in each well was carefully discarded (24)(25).…”