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.
Highlights
Cervical cancer (CC) is one of the most common cancers among females worldwide
spindle and kinetochore-associated complex subunit 3 (SKA3) expression was increased in CC patients and appeared to be a prognostic indicator of CC The SKA3 gene, which is located on chromosome 13q, is associated with mitosis and cancer development
We found the expression of SKA3 mRNA was higher in CC tissue than in normal tissue in both the Biewenga Cervix database (p < 0.001, Fig. 1a) and the Pyeon Multi-cancer database (p < 0.001, Fig. 1b)
Summary
Spindle and kine‐ tochore-associated complex subunit 3 (SKA3), located on chromosome 13q, was identified as a novel gene involved in promoting malignant transformation in cancers. 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. A recent study showed that SKA3 is associated with patient outcome and aggressive disease development in several cancers [15]. By analyzing an Oncomine dataset, we found that SKA3 mRNA expression is higher in CC tissue than in normal tissue and may be associated with survival rate in CC patients. The detailed functions and underlying mechanisms of SKA3 in CC remain largely unknown
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