Polyamine synthesis enzyme AMD1 is closely related to the tumorigenesis and prognosis of human breast cancer

Li, Hanjun; Wang, Jingjie; Xu, Cheng; Zhu, Yueyun; Tuluhong, Dilihumaer; Li, Xinfang; Gao, Hongyu; Li, Jieshou

doi:10.1016/j.yexcr.2022.113235

Cited by 6 publications

(4 citation statements)

References 28 publications

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“…Among the protein-coding genes that we found dysregulated, several genes of interest have already been reported in the literature to be associated with cancer. For instance, in cells overexpressing miR-221, we observed an upregulation of FRAT2, AMD1, and MTHFD1L, genes linked to tumor progression, severity, invasiveness, and worse prognosis [52][53][54][55][56][57][58][59][60]. ENTP6 was found to be downregulated, as previously reported in testicular cancer associated with cisplatin resistance [61].…”

Section: Discussionsupporting

confidence: 82%

miRNA–221 and miRNA–483–3p Dysregulation in Esophageal Adenocarcinoma

Bozzarelli,

Orsini,

Isidori

et al. 2024

Cancers

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Alterations in microRNA (miRNA) expression have been reported in different cancers. We assessed the expression of 754 oncology–related miRNAs in esophageal adenocarcinoma (EAC) samples and evaluated their correlations with clinical parameters. We found that miR–221 and 483–3p were consistently upregulated in EAC patients vs. controls (Wilcoxon signed–rank test: miR–221 p < 0.0001; miR–483–3p p < 0.0001). Kaplan–Meier analysis showed worse cancer–related survival among all EAC patients expressing high miR–221 or miR–483–3p levels (log–rank p = 0.0025 and p = 0.0235, respectively). Higher miR–221 or miR–483–3p levels also correlated with advanced tumor stages (Mann–Whitney p = 0.0195 and p = 0.0085, respectively), and overexpression of miR–221 was associated with worse survival in low–risk EAC patients. Moreover, a significantly worse outcome was associated with the combined overexpression of miR–221 and miR–483–3p (log–rank p = 0.0410). To identify target genes affected by miRNA overexpression, we transfected the corresponding mimic RNA (miRVANA) for either miR–221 or miR–483–3p in a well–characterized esophageal adenocarcinoma cell line (OE19) and performed RNA–seq analysis. In the miRNA–overexpressing cells, we discovered a convergent dysregulation of genes linked to apoptosis, ATP synthesis, angiogenesis, and cancer progression, including a long non–coding RNA associated with oncogenesis, i.e., MALAT1. In conclusion, dysregulated miRNA expression, especially overexpression of miR–221 and 483–3p, was found in EAC samples. These alterations were connected with a lower cancer–specific patient survival, suggesting that these miRNAs could be useful for patient stratification and prognosis.

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Section: Discussionsupporting

confidence: 82%

miRNA–221 and miRNA–483–3p Dysregulation in Esophageal Adenocarcinoma

Bozzarelli,

Orsini,

Isidori

et al. 2024

Cancers

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“…Moreover, 148 mRNAs showed a more than fourfold difference after KLK10 downregulation, and some of these genes are involved in cell growth based on past literatures. Adenosylmethionine decarboxylase 1 (AMD1) has been reported to enhance cell proliferation, induce cell cycle progression, and inhibit apoptosis 42 . Dual‐specificity phosphatase 1 (DUSP1) has also been reported to inhibit cell proliferation, migration and invasion by blocking the JAK2/STAT3 signaling pathway 43 .…”

Section: Discussionmentioning

confidence: 99%

“…Adenosylmethionine decarboxylase 1 (AMD1) has been reported to enhance cell proliferation, induce cell cycle progression, and inhibit apoptosis. 42 Dual‐specificity phosphatase 1 (DUSP1) has also been reported to inhibit cell proliferation, migration and invasion by blocking the JAK2/STAT3 signaling pathway. 43 Based on these results, we considered that KLK10 had an important role in cell proliferation and migration in TEC.…”

Section: Discussionmentioning

confidence: 99%

KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation

Kato,

Noda,

Kobayashi

et al. 2024

Cancer Science

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Tumor endothelial cells (TECs), which are thought to be structurally and functionally different from normal endothelial cells (NECs), are increasingly attracting attention as a therapeutic target in hypervascular malignancies. Although colorectal liver metastasis (CRLM) tumors are hypovascular, inhibitors of angiogenesis are a key drug in multidisciplinary therapy, and TECs might be involved in the development and progression of cancer. Here, we analyzed the function of TEC in the CRLM tumor microenvironment. We used a murine colon cancer cell line (CT26) and isolated TECs from CRLM tumors. TECs showed higher proliferation and migration than NECs. Coinjection of CT26 and TECs yielded rapid tumor formation in vivo. Immunofluorescence analysis showed that coinjection of CT26 and TECs increased vessel formation and Ki‐67+ cells. Transcriptome analysis identified kallikrein‐related peptide 10 (KLK10) as a candidate target. Coinjection of CT26 and TECs after KLK10 downregulation with siRNA suppressed tumor formation in vivo. TEC secretion of KLK10 decreased after KLK10 downregulation, and conditioned medium after KLK10 knockdown in TECs suppressed CT26 proliferative activity. Double immunofluorescence staining of KLK10 and CD31 in CRLM tissues revealed a significant correlation between poor prognosis and positive KLK10 expression in TECs and tumor cells. On multivariate analysis, KLK10 expression was an independent prognostic factor in disease‐free survival. In conclusion, KLK10 derived from TECs accelerates colon cancer cell proliferation and hematogenous liver metastasis formation. KLK10 in TECs might offer a promising therapeutic target in CRLM.

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“…Arginine promotes T-cell proliferation and activation through its metabolism to ornithine via arginase (18). ODC can induce the polarization of M2 macrophages (19).Polyamines metabolic enzymes are frequently dysregulated in tumor cells (20)(21)(22)(23). AMD1 and SMOX are highly expressed in cancer, which is related to poor prognosis of patients and plays a carcinogenic role (24-27).…”

Section: Introductionmentioning

confidence: 99%

Development of a polyamine gene expression score for predicting prognosis and treatment response in clear cell renal cell carcinoma

Chen

Nie²,

Huang³

et al. 2022

Front. Immunol.

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BackgroundsPolyamine metabolism (PM) is closely related to the tumor microenvironment (TME) and is involved in antitumor immunity. Clear cell renal cell carcinoma (ccRCC) not only has high immunogenicity but also has significant metabolic changes. However, the role of PM in the immune microenvironment of ccRCC remains unclear. This study aimed to reveal the prognostic value of PM-related genes (PMRGs) expression in ccRCC and their correlation with the TME.MethodsThe expression levels PMRGs in different cells were characterized with single-cell sequencing analysis. The PMRG expression pattern of 777 ccRCC patients was evaluated based on PMRGs. Unsupervised clustering analysis was used in identifying PMRG expression subtypes, and Lasso regression analysis was used in developing polyamine gene expression score (PGES), which was validated in external and internal data sets. The predictive value of PGES for immunotherapy was validated in the IMvigor210 cohort. Multiple algorithms were used in analyzing the correlation between PGES and immune cells. The sensitivity of PGES to chemotherapeutic drugs was analyzed with the “pRRophetic” package. We validated the genes that develop PGES in tissue samples. Finally, weighted gene co-expression network analysis was used in identifying the key PMRGs closely related to ccRCC, and cell function experiments were carried out.ResultsPMRGs were abundantly expressed on tumor cells, and PMRG expression was active in CD8+ T cells and fibroblasts. We identified three PMRG expression subtypes. Cancer and immune related pathways were active in PMRG expression cluster A, which had better prognosis. PGES exhibited excellent predictive value. The high-PGES group was characterized by high immune cell infiltration, high expression of T cell depletion markers, high tumor mutation burden and tumor immune dysfunction and exclusion, was insensitive to immunotherapy but sensitive to sunitinib, temsirolimus, and rapamycin, and had poor prognosis. Spermidine synthetase (SRM) has been identified as a key gene and is highly expressed in ccRCC at RNA and protein levels. SRM knockdown can inhibit ccRCC cell proliferation, migration, and invasion.ConclusionsWe revealed the biological characteristics of PMRG expression subtypes and developed PGES to accurately predict the prognosis of patients and response to immunotherapy.

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Polyamine synthesis enzyme AMD1 is closely related to the tumorigenesis and prognosis of human breast cancer

Cited by 6 publications

References 28 publications

miRNA–221 and miRNA–483–3p Dysregulation in Esophageal Adenocarcinoma

miRNA–221 and miRNA–483–3p Dysregulation in Esophageal Adenocarcinoma

KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation

Development of a polyamine gene expression score for predicting prognosis and treatment response in clear cell renal cell carcinoma

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