Stable knockdown of protein kinase CK2-alpha (CK2α) inhibits migration and invasion and induces inactivation of hedgehog signaling pathway in hepatocellular carcinoma Hep G2 cells

作者:Wu, Di; Sui, Chengguang; Meng, Fandong; Tian, Xin; Fu, Liye; Li, Yan; Qi, Xinhui; Cui, Huixia; Liu, Yunpeng; Jiang, Youhong*
来源:Acta Histochemica, 2014, 116(8): 1501-1508.
DOI:10.1016/j.acthis.2014.06.001

摘要

Protein kinase CK2-alpha (CK2 alpha), one isoform of the catalytic subunits of serine/threonine kinase CK2, has been indicated to participate in tumorigenesis of various malignancies, including hepatocellular carcinoma (HCC). In the present study, in order to explore the potential role of CK2 alpha in human HCC, we employed short hairpin RNA (shRNA)-mediated RNA interference (RNAi) technology to inhibit the endogenous CK2 alpha expression in HCC cells and established a Hep G2 cell line with stable knockdown of CK2 alpha. Results from wound healing and transwell invasion assays indicated that stable knockdown of CK2 alpha markedly inhibited Hep G2 cell migration and invasion as compared with those transfected with a negative control plasmid. This alteration was accompanied with expression down-regulation of matrix metalloproteinase (MMP)-2, MMP-9, Snail, Slug, Vimentin, and up-regulation of epithelial cadherin (E-cadherin). Moreover, CK2 alpha silencing also induced inactivation of Hedgehog signaling pathway by inhibiting Gli1 and Patched homolog 1 (PTCH1) expressions in HCC cells. Collectively, these results demonstrate that knockdown of CK2 alpha can suppress cell migration and invasion, reduces expression of MMPs, inhibits epithelial-mesenchymal transition (EMT) process and induces inactivation of Hedgehog pathway in HCC cells in vitro. Our study provides in vitro evidence to demonstrate that the pathogenesis of human HCC may be correlated with the high expression of CK2 alpha.