Xu Jun, Song Jianping, Zeng Xinmin, Hu Yanqin, Kuang Jingru
Department of Oncology, Nanchang First Hospital, Nanchang, China.
Department of Thoracic Surgery, Nanchang First Hospital, Nanchang, China.
J Gastrointest Oncol. 2023 Apr 29;14(2):516-532. doi: 10.21037/jgo-23-147.
Hepatocellular carcinoma (HCC) is one of the most common cancers and an important medical problem with poor prognosis. The role of messenger RNA (mRNA) has been broadly researched in the progression of different human cancers. Microarray analysis has demonstrated that kynurenine 3-monooxygenase () expression is lower in HCC, but the mechanism of in regulating the development of HCC remains unknown.
Through comprehensive bioinformatics analysis of GSE101728 and GSE88839, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, protein-protein interaction (PPI) network analysis, gene expression, and overall survival (OS) analysis, was selected as the candidate molecular marker in HCC. The expression of at the protein and RNA level was evaluated by Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, the cell proliferation, migration, invasion, and apoptosis, and the protein levels of epithelial-mesenchymal transition (EMT) markers were examined with Cell Counting Kit 8 (CCK-8) assays, Transwell assay, flow cytometry, and WB.
Through comprehensive bioinformatics analysis, we found that the low expression of KMO in HCC is not conducive to a good prognosis of HCC. Then, through cell experiments, we found that low expression of KMO promoted HCC proliferation, invasion, metastasis, EMT, and cell apoptosis. Additionally, hsa-miR-3613-5p was found to be highly expressed in HCC cells and could negatively regulate the expression of KMO. Moreover, hsa-miR-3613-5p was found to be the target microRNA (miRNA) of according to qRT-PCR verification.
plays an important role in the early diagnosis, prognosis, occurrence, and development of liver cancer, and may target miR-3613-5p to function. This represents a novel insight into understanding the molecular mechanisms of HCC.
肝细胞癌(HCC)是最常见的癌症之一,是一个预后较差的重要医学问题。信使核糖核酸(mRNA)在不同人类癌症进展中的作用已得到广泛研究。微阵列分析表明,犬尿氨酸3-单加氧酶(KMO)在HCC中的表达较低,但KMO调节HCC发展的机制仍不清楚。
通过对GSE101728和GSE88839进行全面的生物信息学分析,包括基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析、蛋白质-蛋白质相互作用(PPI)网络分析、基因表达分析和总生存期(OS)分析,选择KMO作为HCC的候选分子标志物。通过蛋白质印迹法(WB)和定量实时聚合酶链反应(qRT-PCR)评估KMO在蛋白质和RNA水平的表达。此外,使用细胞计数试剂盒8(CCK-8)检测、Transwell检测、流式细胞术和WB检测细胞增殖、迁移、侵袭和凋亡以及上皮-间质转化(EMT)标志物的蛋白质水平。
通过全面的生物信息学分析,我们发现HCC中KMO的低表达不利于HCC的良好预后。然后,通过细胞实验,我们发现KMO的低表达促进了HCC的增殖、侵袭、转移、EMT和细胞凋亡。此外,发现hsa-miR-3613-5p在HCC细胞中高表达,并可负向调节KMO的表达。此外,根据qRT-PCR验证,发现hsa-miR-3613-5p是KMO的靶微小核糖核酸(miRNA)。
KMO在肝癌的早期诊断、预后、发生和发展中起重要作用,可能靶向miR-3613-5p发挥作用。这为理解HCC的分子机制提供了新的见解。