Evaluation of expression of genes CADM1, TWIST1 and CDH1 by immunohistochemestry in melanocytic lesions

Coelho, Karina Munhoz de Paula Alves; Stall, Jaqueline; Júnior, Hercílio Fronza; Blasius, Rodrigo; França, Paulo Henrique Condeixa de

doi:10.1016/j.prp.2017.07.028

Cited by 6 publications

(6 citation statements)

References 21 publications

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“…Recent study has shown that CADM1 could regulate the G1/S transition and represses tumorigenicity through the Rb-E2F pathway in hepatocellular carcinoma [ 50 ]. CADM1 has also been found differentially expressed in melanocytic lesions and had the potential to contribute as an auxiliary tool to the differential diagnosis between nevi and melanomas [ 51 ]. It should be noted that Takao Inoue et al identified CADM1 as a novel, easily detectable cell-membrane protein of OS.…”

Section: Discussionmentioning

confidence: 99%

Circular RNAs hsa_circ_0032462, hsa_circ_0028173, hsa_circ_0005909 are predicted to promote CADM1 expression by functioning as miRNAs sponge in human osteosarcoma

et al. 2018

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BackgroundOsteosarcoma (OS) is a primary malignant bone tumor with a high fatality rate. Many circRNAs have been proved to play important roles in the pathogenesis of some diseases. However, the occurrence of circRNAs in OS remains little known.MethodsThe circular RNA (circRNA) expression file GSE96964 dataset, which included seven osteosarcoma cell lines and one control sample (osteoblast cell line), was downloaded from the Gene Expression Omnibus (GEO) database to explore the potential function of circRNAs in osteosarcoma by competing endogenous RNA (ceRNA) analysis. Three gene expression profiles of OS were downloaded from GEO database and then used for the pathway enrichment analysis, Venn analysis and protein-protein interaction (PPI) network analysis. Real-time qPCR validation and RNA interference were conducted to verify our prediction.ResultsDifferentially expressed circRNAs between OS and control, including 8 up-regulated and 102 down-regulated circRNAs, were generated and ceRNA analysis for 5 most up-regulated or 5 most down-regulated circRNAs in OS were then performed. The pathway enrichment analysis of gene expression profiles indicated differentially expressed genes (DEGs) of three gene profiles significantly enriched in cell cycle pathway, cell adhesion molecules (CAMs) pathway, oxidative phosphorylation pathway, cytokine-cytokine receptor interaction pathway, p53 signaling pathway and proteoglycans in cancer pathway, which were critical important pathways in the pathogenesis of OS. The Venn analysis showed that 2 (one is a pseudogene) up-regulated and 39 down-regulated DEGs were co-expressed in all three gene profiles. Then PPI networks of 41 co-expressed DEGs (up- and down-regulated DEGs) were constructed to predict their functions using the GeneMANIA. The expression levels of these related RNAs also matched our predictions really well.ConclusionUltimately, we found cell adhesion molecule 1 (CADM1) gene was not only a co-expression mRNA of the three mRNA expression profiles of OS, but also are predicted to be regulated by hsa_circ_0032462, hsa_circ_0028173, hsa_circ_0005909 by functioning as miRNAs ‘Sponge’ in human osteosarcoma. These over-expressed circRNAs may result in the over expression of CADM1 which promote the development of OS. We envision this discovery of these important moleculars, incuding hsa_circ_0032462, hsa_circ_0028173, hsa_circ_0005909 and CADM1 may lead to further development of new concepts, thus allowing for more opportunities in diagnosis and therapy of OS.

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Section: Discussionmentioning

confidence: 99%

Circular RNAs hsa_circ_0032462, hsa_circ_0028173, hsa_circ_0005909 are predicted to promote CADM1 expression by functioning as miRNAs sponge in human osteosarcoma

et al. 2018

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“…CADM1 expression is relatively lower in metastatic breast cancer (24) and lung adenocarcinoma (25) patients than in patients with non-invasive cancer. In MM, it was reported that CADM1 expression was significantly downregulated in melanoma tissues (19). Furthermore, CADM1 upregulation inhibited MM cell motility and invasiveness (18).…”

Section: Discussionmentioning

confidence: 99%

“…CADM1, a member of the cell adhesion molecule family, has been proven to be a tumor suppressor in many cancers, including breast cancer (15), esophageal squamous cell carcinoma (16), and hepatocellular carcinoma (17). In MM, it was reported that the expression of CADM1 was also significantly downregulated and functions as a tumor suppressor by suppressing matrix metalloproteinases (MMPs) in MM (18, 19). However, the regulating mechanism of CADM1 in MM is not fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

LNMAT1 Promotes Invasion-Metastasis Cascade in Malignant Melanoma by Epigenetically Suppressing CADM1 Expression

Mou

Zhang

et al. 2019

Front. Oncol.

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The invasion-metastasis cascade is one of the most important factors relating to poor survival and prognosis of malignant melanoma (MM) patients. Long non-coding RNA lymph node metastasis associated transcript 1 (LNMAT1) is a key regulator in lymph node metastasis of multiple cancer types, but the roles and underlying mechanisms of LNMAT1 in the invasion-metastasis cascade of MM remain unclear. In the present study, we aimed to investigate the expression and function of LNMAT1 in MM. Here, we found that LNMAT1 was upregulated in MM tissues and cells, and its expression levels were further enhanced in MM patients with lymph node metastasis and metastatic MM cells. Using loss-of-function assays, we found that LNMAT1 promoted cell migration and invasion and lung metastasis in MM in vitro and in vivo. Moreover, we found that cell adhesion molecule 1 (CADM1), the established tumor suppressor in MM, was the downstream target of LNMAT1. Mechanistically, LNMAT1 epigenetically suppressed CADM1 expression by recruiting EZH2, the key regulator of trimethylation of histone H3 at lysine 27 (H3K27me3), to the CADM1 promoter, resulting in transcriptional inhibition of CADM1. Lastly, rescue assays demonstrated that LNMAT1 promoted cell migration and invasion of MM by suppressing CADM1 expression. Our findings elucidate a new mechanism for LNMAT1-mediated invasion-metastasis cascade in MM and suggest that LNMAT1 may be a new therapeutic target and prognostic predictor for MM.

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“…Paraffin-embedded slices of adult normal brain tissue purchased from the Biochain Institute (Newark, CA, USA) and of four no autopsy derived healthy brain tissues obtained from the Pathology Department of the Catholic University of the Sacred Heart and from Sapienza University in Rome were used as controls. The percentage of positive nuclei in each tumor sample and in the glial population of healthy brain tissues was calculated and results were scored as follows: 0 = nuclear positivity rate: 0–10%; 1 = nuclear positivity rate: 11–25%; 2 = nuclear positivity rate: 26–50%; 3 = nuclear positivity rate: 51–75%; 4 = nuclear positivity rate: 76–100% [ 43 ].…”

Section: Methodsmentioning

confidence: 99%

Loss of miR-107, miR-181c and miR-29a-3p Promote Activation of Notch2 Signaling in Pediatric High-Grade Gliomas (pHGGs)

Catanzaro

Sabato

Russo

et al. 2017

IJMS

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The mechanisms by which microRNAs control pediatric high-grade gliomas (pHGGs) have yet to be fully elucidated. Our studies of patient-derived pHGG tissues and of the pHGG cell line KNS42 revealed down-regulation in these tumors of three microRNAs, specifically miR-107, miR-181c, and miR-29a-3p. This down-regulation increases the proliferation of KNS42 cells by de-repressing expression of the Notch2 receptor (Notch2), a validated target of miR-107 and miR-181c and a putative target of miR-29a-3p. Inhibition (either pharmacologic or genetic) of Notch2 or re-expression of the implicated microRNAs (all three combined but also individually) significantly reduced KNS42 cell proliferation. These findings suggest that Notch2 pathway activation plays a critical role in pHGGs growth and reveal a direct epigenetic mechanism that controls Notch2 expression, which could potentially be targeted by novel forms of therapy for these childhood tumors characterized by high-morbidity and high-mortality.

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Evaluation of expression of genes CADM1, TWIST1 and CDH1 by immunohistochemestry in melanocytic lesions

Cited by 6 publications

References 21 publications

Circular RNAs hsa_circ_0032462, hsa_circ_0028173, hsa_circ_0005909 are predicted to promote CADM1 expression by functioning as miRNAs sponge in human osteosarcoma

Circular RNAs hsa_circ_0032462, hsa_circ_0028173, hsa_circ_0005909 are predicted to promote CADM1 expression by functioning as miRNAs sponge in human osteosarcoma

LNMAT1 Promotes Invasion-Metastasis Cascade in Malignant Melanoma by Epigenetically Suppressing CADM1 Expression

Loss of miR-107, miR-181c and miR-29a-3p Promote Activation of Notch2 Signaling in Pediatric High-Grade Gliomas (pHGGs)

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