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

Cancer Cell International

Wen-bo Niu¹  Ning Deng²  Hai-yan You³  Rong Hu³  Juan Zhong³  Xiao-hui Wu³  Ling-yu Liu³  Lian-bo Wei³  Ming-qing Wang³  Lu Lu⁴  Yang-yang Liu⁵  Ming Wang⁶  Yan-jing Wang⁶ 

[1] Cancer Research Institute, Southern Medical University;School of Traditional Chinese Medicine, Southern Medical University;Shenzhen Hospital, Southern Medical University;The First Affiliated Hospital, Guangzhou University of Chinese Medicine;Zhongshan Huangpu People’s Hospital;Zhujiang Hospital of Southern Medical University;

关键词: SKA3;    Cervical cancer;    Cell proliferation;    Cell cycle;    PI3K/Akt;   

DOI  :  10.1186/s12935-018-0670-4

来源: DOAJ

【 摘 要 】

Abstract Background Cervical 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. Methods In 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. Results SKA3 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. Conclusions We 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.

【 授权许可】

Unknown