간암에서 RNA-binding protein, NONO의 분자적 기능 규명

Abstract

Hepatocellular carcinoma (HCC) has a high incidence and high mortality rates worldwide. However, patients with HCC have limited targeted therapeutic options and the therapies are unsatisfied. Previously published studies have reported that RNA-binding proteins (RBPs) function as oncogenes in tumorigenesis. NONO has been reported to exhibit a variety of molecular roles in human cancers. However, its function in HCC has not yet been completely identified. In the current study, we identified how NONO has a role as an oncogene with molecular function. First, we determined that NONO expression was increased in HCC through the use of diverse, patient-derived HCC datasets and tissues. We found that NONO regulates the expression of genes related to cell cycle control and DNA damage response by using gene expression profiling. Next, our findings suggest that inhibition of NONO expression can reduce the proliferation of HCC cells. We focused on FOXM1 which regulates the progression of DNA replication and the transcription of cell cycle genes in the various NONO-regulated genes. We identified the NONO binding site on FOXM1 and found that it binds directly to the RNA and protein of FOXM1 to regulate the expression and function of FOXM1. The NONO-FOXM1 axis was also found to have a positive correlation and which was found to be significant for predicting the patient survival prognosis. We found that NONO was associated with the DNA damage response and identified the potential for NONO to increase the sensitivity of IR therapy in HCC. In conclusion, our data determined that NONO could regulate HCC proliferation by regulating the expression of genes related to the cell cycle and the DNA damage response and, therefore, significantly predict patient survival in those with HCC.