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अमूर्त

Targeting SOAT1 Ameliorates Hepatocellular Carcinoma by Apoptosis after Comprehensive Analysis for MBOAT Family Genes

Ming Han Wang1 , Ying Jiang2 , Quan Jun Wang1

Background: Despite the largely number of studies on Hepato Cellular Carcinoma (HCC) over past decades, little development had been made because of futile treatment regimens. Here we discussed the expression level, transcriptional and survival data, mutation, and clinical significance of the MBOATs family in patients with HCC to find SOAT1 as a scientific evidence for clinical risk management and decisions effectively. Methods: HCC samples were extracted from the cBioPortal databases; LinkedOmics, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, The Cancer Genome Atlas (TCGA), and R software (×64 3.6.2) were used to comprehensively analyze the roles of MBOATs. p value below to 0.05 was considered statistically significant. TEM imaging, Tunnel, Cell viability and migration assay and so on are also used in this study. Results: In total, 369 HCC tissues and 160 paracancerous tissues were included. The expression levels of MBOAT7, SOAT1, HHAT, DGAT1, and PORCN were higher in HCC tissues than those in normal liver tissue. Gene enrichment analysis revealed that MBOATs played a critical role in apoptosis signaling pathway. Through a comprehensive analysis of the MBOAT family we found a high SOAT1 expression was obviously related with poor OS and DSS in all of the HCC patients, which seemed consistent with the key role of SOAT1 in MBOAT family as a tumor promoter. Genetic inhibition of SOAT1 effectively suppresses tumor growth and induces apoptosis in both in vitro and in vivo. Eventually, we found that targeting SOAT1 promoted ROS production will induce mitochondrial damage and apoptosis in tumor cells and markedly suppressed HCC growth. Conclusions: This is the first time to find the most effective target SOAT1 in the gene family MBOATs. Our results strongly indicated a crucial role of the MBOAT family in HCC, especially SOAT1. SOAT1 could be potential prognostic and predictive markers, and might also function as a potential therapeutic target in HCC by apoptotic pathway induced by ROS and mitochondrial damage