The clinical value and potential molecular mechanism of the downregulation of MAOA in hepatocellular carcinoma tissues

Abstract

Background Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide and tends to be detected at an advanced stage. More effective biomarkers for HCC screening and prognosis assessment are needed and the mechanisms of HCC require further exploration. The role of MAOA in HCC has not been intensively investigated. Methods In‐house tissue microarrays, genechips, and RNAsequencing datasets were integrated to explore the expression status and the clinical value of MAOA in HCC. Immunohistochemical staining was utilized to determine MAOA protein expression. Intersection genes of MAOA related co‐expressed genes and differentially expressed genes were obtained to perform functional enrichment analyses. In vivo experiment was conducted to study the impact of traditional Chinese medicine nitidine chloride (NC) on MAOA in HCC. Results MAOA was downregulated and possessed an excellent discriminatory capability in HCC patients. Decreased MAOA correlated with poor prognosis in HCC patients. Downregulated MAOA protein was relevant to an advanced TNM stage in HCC patients. Co‐expressed genes that positively related to MAOA were clustered in chemical carcinogenesis, where CYP2E1 was identified as the hub gene. In vivo experiment showed that nitidine chloride significantly upregulated MAOA in a nude mouse HCC model. Conclusions A decreased MAOA level is not only correlated with aggressive behaviors in males but also serves as a promising biomarker for the diagnosis and prognosis of HCC patients. Moreover, MAOA may play a role in AFB1 toxic transformation through its synergistic action with co‐expressed genes, especially CYP3A4. MAOA also serves as a potential therapy target of NC in HCC patients.

Down-regulation of microRNA-125b-2-3p is a risk factor for a poor prognosis in hepatocellular carcinoma

“…Our team previously found that NC was a tumor inhibitor in HCC [31][32][33][34][35][36], and in this study, miR-125b-2-3p could be considered a protective factor in HCC. Thus, an in vivo experiment was designed to explore the relationship between NC and miR-125b-2-3p.…”

“…The anti-tumor effects of traditional Chinese medicine in HCC were researched by our team, and we found that nitidine chloride (NC) was an inhibitor of HCC onset and development [31][32][33][34][35][36]. In our study, miR-125b-2-3p was associated with the progression and prognosis of HCC; however, it was still unknown whether NC could act on miR-125b-2-3p.…”

Clinical Significance and Potential Role of LSM4 Overexpression in Hepatocellular Carcinoma: An Integrated Analysis Based on Multiple Databases

“…As a highly malignant tumor with a poor prognosis, hepatocellular carcinoma (HCC) seriously threatens human health and causes a great economic burden to patients and society ( Chen et al, 2016 ; Yan and Fan, 2019 ). Although plenty of studies in recent years have reported a variety of biomarkers for HCC, the currently available are still insufficient ( Pang et al, 2020 ; Xing et al, 2020 ; Cai et al, 2021 ; Dolicka et al, 2021 ). Therefore, it is necessary to identify novel biomarkers for early diagnosis and prognostic monitoring of HCC.…”

The Clinical Significance of Forkhead Box M1 in Esophageal Squamous Cell Carcinoma Tissues: A Study Based on In-house Immunohistochemistry, RNA-sequencing, and Data Mining

“…To reveal the potential signal pathways of differentially expressed FOXM1 in regulating ESCC development, a clusterPro ler package supported by R v3.6.2 was used to predict signal pathways in gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, we listed the genes enriched in the top three KEGG terms and entered them into the search tool to retrieve interacting genes (STRING) to structure the protein-protein interaction (PPI) network as previously reported (34), (35), (36), (37). Next, we downloaded the PPI network analysis result and screened the top nine signi cant hub genes through degree conversion; the CytoHubba module achieved this step in cytoscape v3.7.1.…”