Targeted disruption of S100P suppresses tumor cell growth by down-regulation of cyclin D1 and CDK2 in human hepatocellular carcinoma

Abstract

Abstract. Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The number of cases of HCC has continued to increase in recent decades. Previous studies have suggested that S100P, a member of the S100P calcium-binding protein family, is aberrantly regulated in several malignant neoplasms. However, the underlying molecular mechanisms of the dysregulation of S100P remain to be elucidated. To investigate biological effects of S100P on hepatocarcinogenesis, aberrant expression of S100P was investigated by immunohistochemistry (IHC), Western blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) in HCC tissues and cell lines. Endogenous expression of S100P was disrupted by the RNA interferencemediated protein knockdown method in the human Hep3B liver cancer cell line. Then, cell growth and cellular apoptosis were compared with control siRNA transfectants. The effects of S100P-silencing on the major components of cell cycle regulation were assessed by Western blot analysis. As results, elevated levels of S100P were observed in the HCC tissues compared to the corresponding normal tissues. Targeted disruption of S100P suppressed cell growth and augmented cellular apoptosis. In addition, inhibition of S100P resulted in the down-regulation of cyclinD1 and CDK2. In conclusion, this study showed over-expression of S100P in HCC. The aberrant regulation of S100P in HCC might activate cyclin D1 and CDK expression and contribute to the mitogenic potential of tumor cells during HCC carcinogenesis. These findings provide information that suggests new therapeutic strategies for the treatment of liver cancer.

Roles and Molecular Mechanisms of Biomarkers in Hepatocellular Carcinoma with Microvascular Invasion: A Review

“…Kim et al . 46 found that S100P promoted mitosis of HCC cells by upregulating the expression of cyclin D1 and CDK2, thereby promoting the growth of HCC. In summary, serum S100P level can predict the occurrence of MVI, and S100P may become a new clinical therapeutic target in the future.…”

“…Kim et al . 46 have shown that inhibition of S100P can down-regulate the expression of cyclin D1 and CDK2 in HCC, thereby inhibiting the growth of HCC. Zhang et al .…”

“…In addition, in the study of molecular mechanism, the team found that S100P mediated HCC cell adhesion byCD44-dependent signal transduction and promote the formation of PVTT/MVI. Kim et al 46 found that S100P promoted mitosis of HCC cells by upregulating the expression of cyclin D1 and CDK2, thereby promoting the growth of HCC. In summary, serum S100P level can predict the occurrence of MVI, and S100P may become a new clinical therapeutic target in the future.…”

“…Fan et al 19 found that miR-125b inhibited the metastasis of HCC by inhibiting the expression of suppressor of variegation 3-9 homolog 1 (SUV39H1). Kim et al 46 have shown that inhibition of S100P can down-regulate the expression of cyclin D1 and CDK2 in HCC, thereby inhibiting the growth of HCC. Zhang et al 41 found that inhibition of DDR1 in HCC significantly reduced the migration and invasion of HCC cells.…”

“… 11 found that high expression of PD-L1 in HCC was strongly associated with MVI ( p <0.001). Nevertheless, previous studies have not been able to draw relationships between candidate biomarkers of HCC and MVI, and herein we will review the current understanding of these biomarkers and their association with MVI ( Tables 1 and 2 9 , 12 – 46 ).…”