Dataset Information

Comparative mRNA/micro-RNA co-expression network drives melanomagenesis by promoting epithelial-mesenchymal transition and vasculogenic mimicry signaling.

ABSTRACT: This study aimed to identify a novel disease-associated differentially co-expressed mRNA-microRNA (miRNA) that is associated with vasculogenic mimicry (VM) and epithelial-to-mesenchymal transition (EMT) network at different stages of melanoma. By applying weighted gene co-expression network analysis, we constructed a VM+EMT biological network with the available microarray dataset downloaded from a public database. Quantitative real-time PCR, immunohistochemical staining, and CD31-periodic acid solution dual staining were performed to confirm the expression of genes associated with EMT and VM formation in subjects with malignant melanoma (n = 18) and primary melanoma (n = 13) and in healthy subjects (n = 10). Our findings suggested that phosphatidylserine-specific phospholipase A1-alpha (PLA1A) and dermokine (DMKN) genes function as oncogenes that trigger VM and EMT processes during melanomagenesis on interaction with miR-370, miR-563, and miR-770-5p. PLA1A and DMKN genes can be considered potential VM+EMT network-based diagnostic biomarkers for distinguishing between melanoma patients. We postulate that a network with altered PLA1A/miR-563 and DMNK/miR-770-5p/miR-370 may contribute to melanomagenesis by triggering the EMT signaling pathway and VM formation. This study provides a potentially valuable approach for the early diagnosis and prognosis of melanoma progression.

SUBMITTER: He W

PROVIDER: S-EPMC8512639 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Comparative mRNA/micro-RNA co-expression network drives melanomagenesis by promoting epithelial-mesenchymal transition and vasculogenic mimicry signaling.

He WenFeng W Yang Gang G Liu Shuya S Maghsoudloo Mazaher M Shasaltaneh Marzieh Dehghan MD Kaboli Parham Jabbarzadeh PJ Zhang Cuiwei C Zhang JingHeng J Entezari Maliheh M Imani Saber S Wen QingLian Q

Translational oncology 20211006 12

This study aimed to identify a novel disease-associated differentially co-expressed mRNA-microRNA (miRNA) that is associated with vasculogenic mimicry (VM) and epithelial-to-mesenchymal transition (EMT) network at different stages of melanoma. By applying weighted gene co-expression network analysis, we constructed a VM+EMT biological network with the available microarray dataset downloaded from a public database. Quantitative real-time PCR, immunohistochemical staining, and CD31-periodic acid s ...[more]

PMID: 34626953

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Project description:Choriocarcinoma (CC) is characterized by earlier blood metastasis compared with other female genital tumors and a high incidence of massive hemorrhage. Vasculogenic mimicry (VM) is highly associated with metastasis, and syncytiotrophoblast is involved in the formation of VM in CC. Forskolin is a typical activator of the cAMP pathway, which is involved in the syncytiolization of trophoblastic cells. In the present study, to determine the effects and mechanism of forskolin on cell invasion and VM during syncytiolization in vitro and in vivo, JEG?3 and JAR cell lines were treated with 100 µM forskolin for 48 h, and wound healing and invasion assays were used to verify cell migratory and invasive capacities. A 3D culture and tube formation assays were established to detect VM. Variation of morphology and markers of the epithelial?to?mesenchymal transition (EMT) were assessed, and the role of the Notch signaling pathway was investigated in CC cells treated with forskolin. The results of the present study demonstrated that 100 µM forskolin induced syncytiolization of trophoblastic cells and enhanced the migratory and invasive abilities of JEG?3 and JAR cell lines. In addition, the capacity of VM was significantly increased, whereas tube formation ability was decreased by forskolin in vitro and in vivo compared with the respective control groups. The cellular morphology exhibited EMT during the syncytiolization process, which was further supported by the changes in EMT marker expression, including downregulation of E?cadherin and cytokeratin and upregulation of N?cadherin, vimentin and zinc finger E?box?binding homeobox 1. The Notch?1 signaling pathway was activated to induce EMT in forskolin?induced VM process in CC cells, and VM and EMT could be reversed by using the ??secretase inhibitor DAPT to block the Notch?1 pathway. Overall, the results of the present study demonstrated that forskolin enhanced the capacity of VM formation and metastasis through Notch?1?activated EMT in the syncytiolization of trophoblastic cells.

Dataset Information

Comparative mRNA/micro-RNA co-expression network drives melanomagenesis by promoting epithelial-mesenchymal transition and vasculogenic mimicry signaling.

Publications

Comparative mRNA/micro-RNA co-expression network drives melanomagenesis by promoting epithelial-mesenchymal transition and vasculogenic mimicry signaling.

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