Molecular mechanism of CK19 involved in the regulation of postoperative recurrence of HBV-associated primary hepatocellular carcinoma in Guangxi

BACKGROUND: Cytokeratin 19 (CK19/KRT19) is a marker of biliary epithelial cells and hepatic progenitor cells, which can be expressed in some hepatocellular carcinoma (HCC). However, its role in the occurrence, development, and recurrence of hepatitis B virus (HBV)-associated HCC remains to be clarified. This study is to analyze the relationship between the expression of CK19 protein and clinicopathological factors, as well as the effect of positive CK19 expression on the prognosis of HCC patients. METHODS: Small interfering RNA (siRNA) transfection was used to silence CK19 in MHCC-97H and Hep-3B. Real time polymerase chain reaction (qPCR), immunohistochemistry (IHC), and flow cytometry were used to detect the effects of CK19 silencing on cell function. High-throughput sequencing was used to explore the potential molecular mechanism of CK19 positive expression of HCC. RESULTS: In 24 patients with HCC, CK19 was only expressed in cancer tissues, regardless of primary or recurrent tumors, and the positive expression rate of recurrent tumors was higher than that of primary tumors. The HCC participants with positive primary CK19 expression had a shorter tumor-free survival time. Silencing of the CK19 gene in MHCC-97H and Hep-3B attenuated the migration and invasion ability of MHCC-97H, increased the G2 phase cell content of MHCC-97H and Hep-3B, and increased the proportion of apoptosis. High-throughput sequencing results suggested that changes in the function of the cell cycle regulating genes, drug, and carcinogenic metabolism might be the potential pathways of CK19 in regulating the biological behavior of HCC. CONCLUSIONS: Among HBV-related recurrent HCC, the positive rate of CK19 expression in recurrent HCC tumors was higher, and the tumor-free survival time of HCC patients with positive CK19 expression in primary HCC was shorter. After silencing of the CK19 gene, the migration and invasion ability of HCC cells were weakened, the content of G2-M cell cycle cells was increased, the invasion and migration of HCC cells were inhibited, and apoptosis was promoted. Changes in the function of the cell cycle regulating genes and the regulation of drug and carcinogenic metabolites-related pathways may be the pathways through which CK19 affects the biological behavior of HCC.