Down regulated oncogene inhibits growth, invasion, and metastasis of hepatocellular carcinoma through the Ras/MAPK signaling pathway and epithelial-to-mesenchymal transition.

BACKGROUND

Hepatocellular carcinoma (HCC) is the leading cause of cancer death. Kinesin family member 2C () has been shown as oncogene in a variety of tumors. However, its role in HCC remains unclear.

METHODS

In this study, the expression level of KIF2C in HCC was detected by immunohistochemical staining and RT-PCR, and verified by Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Oncomine database. A curve was established to evaluate the diagnostic efficiency of . The effect of on HCC was investigated by flow cytometry, Cell Counting Kit-8, Transwell, and the wound-healing assay. We explored the underlying mechanism through epithelial-to-mesenchymal transition (EMT) and transcriptome sequences analysis.

RESULTS

KIF2C was overexpression in HCC tissue and related to neoplasm histologic grade (P<0.001), pathology stage (P=0.001), and a dismal prognosis (overall, recurrence-free, and disease-free survival). The diagnostic efficacy of was >90% in diagnosing HCC. The HCC cell function experiments showed that KIF2C promoted HCC cell proliferation, migration, invasion, and an accelerated cell cycle, and inhibited apoptosis. Based on western blot analysis and RT-PCR, we found that KIF2C promoted HCC invasion and metastasis through activation of the EMT. Based on transcriptome sequences, we showed that promoted HCC through the Ras/MAPK and PI3K/Akt signaling pathway.

CONCLUSIONS

was found to promote the progression of HCC and is anticipated to serve as a biomarker for HCC diagnosis, prognosis, and targeted therapy.