Inhibition of RNaseH2A Induces Fas-Regulated Programmed Cell Death in Hepatoma Cells

Objective: To screen clinically significant potential drug targets in liver cancer and to study the function and potential molecular mechanisms of this target protein in the development of liver cancer. Methods: By using the clinical database GEPIA to find genes that are differentially expressed in liver cancer compared to normal tissues, we further screened the genes that are highly expressed in hepatocellular carcinoma and have clinical prognostic relevance. Heat maps were used to sort these genes according to their clinical prognostic relevance, so as to screen for the target gene of interest. The characteristics of target gene expression and clinical prognosis in hepatocellular carcinoma were studied. The target gene was knocked down through siRNA, and cell proliferation experiments and apoptosis experiments were used to verify the importance of the target gene in the occurrence and development of liver cancer. Finally, we elucidated the potential molecular mechanism of the target gene’s function in liver cancer based on the mutual regulatory relationship between the target gene and key apoptosis genes. Results: 1482 genes were significantly underexpressed in liver cancer, and 725 genes were significantly overexpressed in liver cancer, of which RNaseH2A was significantly overexpressed in liver cancer and had a significant clinical prognosis. Knockdown of RNaseH2A inhibited the proliferation of hepatocellular carcinoma cells and induced apoptosis. Knockdown of RNaseH2A induced the high expression of Fas, a key gene for apoptosis, and liver cancer usually features low expression of Fas. After hepatocellular carcinoma cells that were knocked down of RNaseH2A continued were subject to Fas knockdown, hepatocellular carcinoma cell proliferation and apoptosis returned to normal levels. Conclusion: The high expression of RNaseH2A regulates the low expression of Fas, a key gene for apoptosis, thereby inhibiting apoptosis, promoting cell proliferation, and participating in the development of liver cancer.