Kinesin family members KIF2C/4A/10/11/14/18B/20A/23 predict poor prognosis and promote cell proliferation in hepatocellular carcinoma

Am J Transl Res. 2020 May 15;12(5):1614-1639. eCollection 2020.

Abstract

Kinesin superfamily proteins (KIFs) comprise a family of molecular motors that transport membranous organelles and protein complexes in a microtubule- and ATP-dependent manner, with multiple roles in cancers. Little is known about the function of KIFs in hepatocellular carcinoma (HCC). Here, we investigate the roles of KIFs in the prognosis and progression of HCC. Upregulation of eight KIFs (KIF2C, KIF4A, KIF10, KIF11, KIF14, KIF18B, KIF20A, and KIF23) was found to be significantly associated with the tumor stage and pathological tumor grade of HCC patients. Additionally, a high expression of these eight KIFs was significantly associated with shorter overall survival (OS) and disease-free survival (DFS) in patients with HCC. Cox regression analysis showed the mRNA expression levels of these eight KIF members to be independent prognostic factors for worse outcomes in HCC. Moreover, a risk score model based on the mRNA levels of the eight KIF members effectively predicted the OS rate of patients with HCC. Additional experiments revealed that downregulation of each of the eight KIFs effectively decreased the proliferation and increased the G1 arrest of liver cancer cells in vitro. Taken together, these results indicate that KIF2C/4A/10/11/14/18B/20A/23 may serve as prognostic biomarkers for survival and potential therapeutic targets in HCC patients.

Keywords: Hepatocellular carcinoma; KIFs; cell cycle; migration; prognosis; proliferation.