NSUN3-Mediated ROS Accumulation Promotes Hepatocellular Carcinoma Proliferation and Activates PI3K/AKT Pathway.

Abstract

NSUN3 (NOP2/Sun RNA methyltransferase family member 3) is a gene encoding an RNA methyltransferase primarily responsible for specific methylation modifications on mitochondrial tRNA. Recent studies have indicated that aberrant expression of NSUN3 may be associated with the development of a range of tumors. UALCAN and GEPIA2 were utilized for bioinformatics analyses, while lentiviral vectors and small interfering RNA techniques were employed to create cell lines with either overexpression or silencing of NSUN3. To assess the impact of NSUN3 on hepatocellular carcinoma cells in vitro, CCK-8 assays, apoptosis assays, and cell cycle analyses were conducted. The accumulation of ROS mediated by NSUN3 was evaluated using fluorescent probes specific for ROS. Additionally, Western blotting was performed to verify transfection efficiency and to analyze the expression levels of the PI3K/AKT signaling pathway and BCL-2 protein. The findings of the current investigation indicate that NSUN3 is markedly overexpressed in HCC and is associated with a negative prognosis. The role of NSUN3 in modulating mitochondrial energy metabolism implies that its overexpression may facilitate the proliferation of HCC cells through the promotion of ROS accumulation. In contrast, the silencing of NSUN3 has been demonstrated to hinder the proliferation of HCC cells. Furthermore, the results also indicate that NSUN3 has the capacity to activate the PI3K/AKT signaling pathway, this resulted in the preliminary clarification of the molecular mechanisms at play. In summary, our research addresses the functional role of NSUN3 in HCC. The initial identification of NSUN3 suggests that it may serve as a promising target for the development of novel therapeutic strategies in the treatment of HCC.