Upregulation of SKA3 enhances cell proliferation and correlates with poor prognosis in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most aggressive types of malignancy worldwide. However, the mechanism underlying its frequent recurrence remains unclear. Studies have demonstrated that spindle and kinetochore associated complex subunit 3 (SKA3) is highly expressed in colorectal and prostate cancer. The present study aimed to determine whether SKA3 could be a predictive and prognostic marker for liver cancer. SKA3 expression levels in liver cancer cell lines, liver cancer tissues, normal liver cells and non-cancerous tissues were compared at both transcriptional and translational levels. Correlation between SKA3 levels, clinicopathological characteristics and patient survival was also assessed. Gene set enrichment analysis (GSEA) was performed to identify SKA3-associated pathways. Furthermore, SKA3 was knocked down and overexpressed in liver cancer cells, and then assessed the effect on cell proliferation, cell cycle, and tumor formation ability. Kaplan-Meier survival analysis and log-rank test were used to evaluate the association between SKA3 expression levels and prognosis. SKA3 mRNA and protein expression levels were significantly higher in liver cancer cell lines and clinical samples, compared with normal controls. Immunohistochemical analysis of 110 patients revealed that upregulation of SKA3 correlated with clinical pathological characteristics and patient survival. GSEA showed that BENPORATH_PROLIFERATION gene set signaling pathways were correlated with SKA3 expression levels. Luciferase reporter activity assay revealed that knockdown of SKA3 significantly inhibited the activity of transcription factor E2F. Downregulation of SKA3 significantly inhibited cell proliferation, cell cycle arrest in G(1)-S phase and tumorigenesis both in vitro and in vivo, decreased the expression levels of cyclin D1 and phosphorylated-retinoblastoma and increased those of p21, suggesting a potential role of SKA3 in mediating tumor cell cycle and progression. SKA3 may function as an oncogene in liver cancer and may be a promising prognostic biomarker and candidate for targeted therapy.