• Anticancer therapy
• Cancer
• Drug resistance
• MAO inhibitors
• Monoamine oxidases

• Humans
• Monoamine Oxidase Inhibitors/pharmacology
• Monoamine Oxidase Inhibitors/chemistry
• Monoamine Oxidase Inhibitors/therapeutic use
• Neoplasms/drug therapy
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/chemistry
• Antineoplastic Agents/therapeutic use
• Monoamine Oxidase/metabolism
• Animals
• Molecular Structure

• Humans
• Female
• Breast Neoplasms/pathology
• Breast Neoplasms/metabolism
• Phyllodes Tumor/pathology
• Phyllodes Tumor/metabolism
• Phyllodes Tumor/enzymology
• Adult
• Middle Aged
• Biomarkers, Tumor/metabolism
• Young Adult
• Monoamine Oxidase/metabolism
• Monoamine Oxidase/analysis
• Monoamine Oxidase/biosynthesis
• Aged
• Adolescent
• Disease-Free Survival
• Immunohistochemistry
• Tissue Array Analysis
• Protein-Lysine 6-Oxidase/metabolism
• Prognosis
• Neoplasm Recurrence, Local/pathology

• Cancer
• Drug repurposing
• MAO inhibitors
• Monoamine oxidase (MAO)

• Biomarker
• Metabolomics
• Pathways
• Transcriptomics
• Triple-negative breast cancer

• Humans
• Triple Negative Breast Neoplasms/genetics
• Triple Negative Breast Neoplasms/blood
• Triple Negative Breast Neoplasms/metabolism
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Biomarkers, Tumor/blood
• Metabolomics
• Female
• Gene Expression Regulation, Neoplastic
• Transcriptome/genetics
• Gene Expression Profiling
• Middle Aged
• Gene Regulatory Networks
• Case-Control Studies
• ROC Curve
• Reproducibility of Results
• Metabolic Networks and Pathways/genetics
• Metabolome/genetics
• Adult

• 2021J01278 Natural Science Foundation of Fujian Province
• NSFC 62072107 National Natural Science Foundation of China

• biomarker
• cancer
• cancer therapy
• monoamine oxidase
• monoamine oxidase inhibitor

• biomarkers
• endometrial cancer
• extracellular vesicles
• secretome

• Humans
• Female
• Endometrial Neoplasms/metabolism
• Endometrial Neoplasms/pathology
• Extracellular Vesicles/metabolism
• Proteome/metabolism
• Proteome/analysis
• Obesity/metabolism
• Obesity/pathology
• Biomarkers, Tumor/metabolism
• Proteomics/methods
• Body Mass Index
• Middle Aged

• Antitumor chemotherapy
• Inhibitors
• Monoamine oxidase
• Neuroprotection
• Tumorigenesis

• Humans
• Monoamine Oxidase Inhibitors/pharmacology
• Monoamine Oxidase Inhibitors/therapeutic use
• Monoamine Oxidase/metabolism
• Parkinson Disease/drug therapy

• Male
• Humans
• Monoamine Oxidase Inhibitors/pharmacology
• Breast Neoplasms/drug therapy
• Breast Neoplasms/genetics
• Monoamine Oxidase/genetics
• Monoamine Oxidase/metabolism
• Oxidative Stress
• Reactive Oxygen Species/metabolism

• Clorgyline
• Drug design
• Enzalutamide
• MAOI
• Neurotoxicity
• Prostate cancer
• SAR
• Synthesis

• Humans
• Male
• Antidepressive Agents
• Brain/metabolism
• Caco-2 Cells
• Clorgyline/pharmacology
• Monoamine Oxidase/metabolism
• Monoamine Oxidase Inhibitors/pharmacology
• Prostatic Neoplasms/drug therapy

• Biomarker
• Colon cancer
• activated fibroblast

• Humans
• Transforming Growth Factor beta1/metabolism
• Fibroblasts/pathology
• Colorectal Neoplasms/pathology
• Actins/metabolism
• Biomarkers/metabolism
• Cancer-Associated Fibroblasts/metabolism

• adrenal cortical tumor
• adrenal gland tumor
• amine oxidase protein
• pheochromocytoma

• Bevacizumab
• Metabolism-associated gene
• Ovarian cancer
• Prognosis
• risk factor

• Humans
• Female
• Prognosis
• Ovarian Neoplasms/genetics

• LINC00839
• m6A
• nasopharyngeal carcinoma
• progression

• Androgen receptor
• Drug resistance
• Immunotherapy
• Metastasis

• antiandrogen therapy
• castration resistance
• metastasis
• monoamine oxidase A
• prostate cancer
• tumor-stromal interaction

Amine oxidase copper containing 1 (AOC1) is a copper-containing amine oxidase that catalyzes the deamination of polyamines. AOC1 functions as an oncogene in human gastric cancer. There is little information available regarding the function of AOC1 in hepatocellular carcinoma (HCC). In the present study, reverse transcription-quantitative PCR was used to detect the expression levels of AOC1 in HCC tissues, and the role of AOC1 in HCC progression was determined using western blot, Cell Counting Kit 8, clone formation, wound-healing and Transwell assays. An AOC1 survival curve was generated with data downloaded from The Cancer Genome Atlas, and Gene Set Enrichment Analysis was performed to investigate the potential biological mechanisms of AOC1 in HCC. AOC1 was found to be upregulated in HCC tissues, which was associated with a poor prognosis. Furthermore, AOC1-knockdown inhibited HCC cell proliferation, migration and invasiveness, suppressed IL-6 expression, as well as decreasing JAK2 and STAT3 phosphorylation. Ultimately, the results of the present study illustrate that AOC1 promoted the proliferation, migration and invasiveness of HCC cells by regulating the IL-6/JAK/STAT3 pathway.

• IL-6/JAK/STAT3
• amine oxidase copper containing 1
• epithelial-mesenchymal transition
• invasion
• migration
• proliferation

Monoamine oxidases (MAOs) are oxidative enzymes that catalyze the conversion of biogenic amines into their corresponding aldehydes and ketones through oxidative deamination. Owing to the crucial role of MAOs in maintaining functional levels of neurotransmitters, the implications of its distorted activity have been associated with numerous neurological diseases. Recently, an unanticipated role of MAOs in tumor progression and metastasis has been reported. The chemical inhibition of MAOs might be a valuable therapeutic approach for cancer treatment. In this review, we reported computational approaches exploited in the design and development of selective MAO inhibitors accompanied by their biological activities. Additionally, we generated a pharmacophore model for MAO-A active inhibitors to identify the structural motifs to invoke an activity.

• QSAR
• cancer
• inhibitors
• metastasis
• monoamine oxidase
• pharmacophore

• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Computational Biology
• Drug Design
• Drug Development
• Humans
• Monoamine Oxidase
• Monoamine Oxidase Inhibitors/pharmacology
• Monoamine Oxidase Inhibitors/therapeutic use
• Neoplasms/drug therapy
• Neoplasms/enzymology
• Quantitative Structure-Activity Relationship

Lung cancer remains notorious for its poor prognosis. Despite the advent of tyrosine kinase inhibitors and immune checkpoint inhibitors, the probability of curing the disease in lung cancer patients remains low. Novel mechanisms and treatment strategies are needed to provide hope to patients. Advanced strategies of next generation sequencing (NGS) and bioinformatics were used to analyze normal and lung cancer tissues from lung cancer patients. Amine oxidases have been linked to leukocyte migration and tumorigenesis. However, the roles of amine oxidases in lung cancer are not well-understood. Our results indicated that amine oxidase, copper containing 3 (AOC3) was significantly decreased in the tumor tissue compared with the normal tissue, at both the mRNA and protein level, in the included lung cancer patients and public databases. Lower expression of AOC3 conferred a poorer survival probability across the different cohorts. Epigenetic silencing of AOC3 via miR-3691-5p caused tumor promotion and progression by increasing migration and epithelial-mesenchymal transition (EMT). Furthermore, knockdown of AOC3 caused less CD4⁺ T-cell attachment onto lung cancer cells and reduced transendothelial migration in vitro, as well as reducing CD4⁺ T-cell trafficking to the lung in vivo. In conclusion, the present study revealed that downregulation of AOC3 mediated lung cancer promotion and progression, as well as decrease of immune cell recruitment. This novel finding could expand our understanding of the dysregulation of the tumor immune microenvironment and could help to develop a novel strategy for the treatment of lung cancer.

• AOC3
• EMT
• lung cancer
• microRNA-3691-5p
• tumor immune microenvironment

• BC, breast cancer
• Bax, Bcl-2-associated X
• Bcl2, B-cell lymphoma 2
• CAF, cyclophosphamide, doxorubicin, and fluorouracil
• CASP3
• CMF, cyclophosphamide, methotrexate, and fluorouracil
• Chemotherapy
• DC, docetaxel and capecitabine
• ER+ ductal carcinoma
• ER, estrogen receptor
• ERBB2 (HER2)
• FC, fold-change
• FU, fluorouracil
• GSR
• H2O2, hydrogen peroxide
• HER2, human epidermal growth factor 2
• IGF-1, insulin-like growth factor-1
• NOX4
• OH●, hydroxyl radical
• PI3K/Akt, phosphatidylinositol 3-kinase/protein kinase B
• PM, personalized medicine
• PR, progesterone receptor
• PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses
• ROS, reactive oxygen species
• TGF-α/β, transforming growth factor alpha/beta
• TMX, tamoxifen
• TS, thymidylate synthase

• cancer immunotherapy
• tumour immunology

• Animals
• Breast Neoplasms/genetics
• Breast Neoplasms/metabolism
• Breast Neoplasms/mortality
• Cell Line, Tumor
• Drug Synergism
• Female
• Gene Expression Regulation, Neoplastic/drug effects
• Gene Expression Regulation, Neoplastic/genetics
• Humans
• Immunotherapy/methods
• Kaplan-Meier Estimate
• Lymphoma/genetics
• Lymphoma/metabolism
• Lymphoma/mortality
• Melanoma/genetics
• Melanoma/metabolism
• Melanoma/mortality
• Mice
• Mice, Inbred C57BL
• Monoamine Oxidase/deficiency
• Monoamine Oxidase/genetics
• Monoamine Oxidase/metabolism
• Monoamine Oxidase Inhibitors/pharmacology
• Monoamine Oxidase Inhibitors/therapeutic use
• Neoplasms/drug therapy
• Neoplasms/genetics
• Neoplasms/immunology
• Neoplasms/mortality
• Ovarian Neoplasms/genetics
• Ovarian Neoplasms/metabolism
• Ovarian Neoplasms/mortality
• Programmed Cell Death 1 Receptor/antagonists & inhibitors
• Programmed Cell Death 1 Receptor/metabolism
• RNA-Seq
• Reactive Oxygen Species/metabolism
• Single-Cell Analysis
• T-Lymphocytes/immunology
• Tumor-Associated Macrophages/drug effects
• Tumor-Associated Macrophages/metabolism
• Xenograft Model Antitumor Assays

• P30 CA016042 NCI NIH HHS
• P50 CA211015 NCI NIH HHS
• T32 CA009120 NCI NIH HHS
• T32 GM008042 NIGMS NIH HHS
• Stop Cancer
• Tower Cancer Research Foundation (TCRF)
• U.S. Department of Health & Human Services | National Institutes of Health (NIH)
• Rose Hills Research Foundation (BSCRC-RHF Research Award), Ablon Foundation (Ablon Scholars Award), UCLA BSCRC (Predoctoral Fellowship), Whitcome Foundation (Whitcome Predoctoral Fellowship).

• Alzheimer’s disease
• Biomarkers
• cancer
• chronic kidney disease
• periodontitis
• polyamines

• Breast cancer
• Module selection
• Prognosis
• Weighted gene co-expression network

• breast cancer
• lncRNA
• mRNA
• prognostic markers
• weighted gene coexpression network analysis

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.

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.

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.

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.

• MAOA
• HCC
• RNA-seq
• gene chip
• immunohistochemical staining
• tissue microarray

Gastric carcinoma (GC) is one of the most aggressive primary digestive cancers. It has unsatisfactory therapeutic outcomes and is difficult to diagnose early.

To identify prognostic biomarkers for GC patients using comprehensive bioinformatics analyses.

Differentially expressed genes (DEGs) were screened using gene expression data from The Cancer Genome Atlas and Gene Expression Omnibus databases for GC. Overlapping DEGs were analyzed using univariate and multivariate Cox regression analyses. A risk score model was then constructed and its prognostic value was validated utilizing an independent Gene Expression Omnibus dataset (GSE15459). Multiple databases were used to analyze each gene in the risk score model. High-risk score-associated pathways and therapeutic small molecule drugs were analyzed and predicted, respectively.

A total of 95 overlapping DEGs were found and a nine-gene signature (COL8A1, CTHRC1, COL5A2, AADAC, MAMDC2, SERPINE1, MAOA, COL1A2, and FNDC1) was constructed for the GC prognosis prediction. Receiver operating characteristic curve performance in the training dataset (The Cancer Genome Atlas-stomach adenocarcinoma) and validation dataset (GSE15459) demonstrated a robust prognostic value of the risk score model. Multiple database analyses for each gene provided evidence to further understand the nine-gene signature. Gene set enrichment analysis showed that the high-risk group was enriched in multiple cancer-related pathways. Moreover, several new small molecule drugs for potential treatment of GC were identified.

The nine-gene signature-derived risk score allows to predict GC prognosis and might prove useful for guiding therapeutic strategies for GC patients.

• Gastric carcinoma
• Bioinformatic analysis
• Prognosis
• Overall survival
• Differentially expressed genes

AOC1 is a copper-containing amine oxidase that is responsible for catalyzing the deamination of polyamines, which produces reactive oxygen species. Previous studies have demonstrated that polyamines are involved in the regulation of proliferation, migration, and apoptosis of cells. However, very little is known about the functions and regulatory mechanisms of AOC1 in tumors.

Based on GEPIA data, we found that AOC1 was significantly upregulated in human gastric cancer tissues. We knocked down AOC1 in human AGS and MKN45 cells using siRNA transfection, then utilized qRT-PCR assay and Western blot to verify the effectiveness of AOC1 knockdown in gastric cancer cells.

Function analysis demonstrated that knockdown of AOC1 inhibited the proliferation, invasion, and migration of human gastric cancer cells. Flow cytometry detection suggested that AOC1 knockdown induced apoptosis in human gastric cancer cells. Mechanism investigation suggested that AOC1 knockdown increased the ratio of Bax/Bcl2 and induced activation of the caspase cascade. Furthermore, the AKT signaling pathway was inactivated when AOC1 was silenced, including downregulated phosphorylation level of AKT and expression of downstream effectors, Cyclin D1, and p70S6K. Finally, we found that knockdown of AOC1 inhibited the epithelial–mesenchymal transition (EMT) in human gastric cancer by increasing the expression of epithelial markers E-cadherin, as well as decreasing mesenchymal marker N-cadherin, SNAIL and Slug.

Our study suggests that AOC1 functions as an oncogene in human gastric cancer by activating the AKT signaling pathway and EMT process and maybe a target of 6-mercaptopurine, which provides new insight in the clinical use of AOC1 in gastric cancer therapy.

• AKT
• AOC1
• apoptosis
• epithelial-mesenchymal transition
• invasion and migration
• proliferation

Breast tumor growth and recurrence are driven by an infrequent population of breast tumor-initiating cells (BTIC). We and others have reported that the frequency of BTIC is orders of magnitude higher when breast tumor cells are propagated in vitro as clonal spheres, termed tumorspheres, by comparison to adherent cells. We exploited the latter to screen > 35,000 small molecules to identify agents capable of targeting BTIC. We unexpectedly discovered that selective antagonists of serotonin signaling were among the hit compounds. To better understand the relationship between serotonin and BTIC we expanded our analysis to include monoamine oxidase-A (MAO-A), an enzyme that metabolizes serotonin.

We used the Nanostring technology and Western blotting to determine whether MAO-A is expressed in human breast tumor cell lines cultured as tumorspheres by comparison to those grown as adherent cells. We then determined whether MAO-A activity is required for tumorsphere formation, a surrogate in vitro assay for BTIC, by assessing whether selective MAO-A inhibitors affect the frequency of tumorsphere-forming cells. To learn whether MAO-A expression in breast tumor cells is associated with other reported properties of BTIC such as anticancer drug resistance or breast tumor recurrence, we performed differential gene expression analyses using publicly available transcriptomic datasets.

Tumorspheres derived from human breast tumor cell lines representative of every breast cancer clinical subtype displayed increased expression of MAO-A transcripts and protein by comparison to adherent cells. Surprisingly, inhibition of MAO-A activity with selective inhibitors reduced the frequency of tumorsphere-forming cells. We also found that increased MAO-A expression is a common feature of human breast tumor cell lines that have acquired anticancer drug resistance and is associated with poor recurrence-free survival (RFS) in patients that experienced high-grade, ER-negative (ER⁻) breast tumors.

Our data suggests that MAO-A activity is required for tumorsphere formation and that its expression in breast tumor cells is associated with BTIC-related properties. The discovery that a selective MAO-A inhibitor targets tumorsphere-forming cells with potencies in the nanomolar range provides the first evidence of this agent’s anticancer property. These data warrant further investigation of the link between MAO-A and BTIC.

• Breast tumor-initiating cells
• Monoamine oxidase-A
• Tumorspheres

• Buffalo
• Coagulation
• Complement
• Fasciola gigantica
• Lysozyme
• PRM
• iTRAQ

Monoamine oxidase A (MAOA) is an important mitochondria-bound enzyme that catalyzes the oxidative deamination of monoamine neurotransmitters. Accumulating evidence suggests a significant association of increased MAOA expression and advanced high-grade prostate cancer (PCa) progression and metastasis. Herein, a series of novel conjugates combining the MAOA inhibitor isoniazid (INH) and tumor-targeting near-infrared (NIR) heptamethine cyanine dyes were designed and synthesized. The synthesized compounds G1–G13 were evaluated in vitro for their cytotoxicity against PC-3 cells using the MTT assay, and molecular docking studies were performed. Results showed that most tested compounds exhibited improved antitumor efficacy compared with INH. Moreover, conjugates G10 and G11 showed potent anticancer activity with IC₅₀ values (0.85 and 0.4 μM respectively) comparable to that of doxorubicin (DOX). This may be attributable to the preferential accumulation of these conjugates in tumor cells. G10, G11, and G12 also demonstrated moderate MAOA inhibitory activities. This result and the results of molecular docking studies were consistent with their cytotoxicity activities. Taken together, these data suggest that a combination of the MAOA inhibitor INH with tumor-targeting heptamethine cyanine dyes may prove to be a highly promising tool for the treatment of advanced prostate cancer.

• heptamethine cyanine dyes
• isoniazid
• molecular docking
• monoamine oxidase A
• prostate cancer