Potential Anti-Metastatic Role of the Novel miR-CT3 in Tumor Angiogenesis and Osteosarcoma Invasion

Autor:	Lavinia Raimondi, Alessia Gallo, Nicola Cuscino, Angela De Luca, Viviana Costa, Valeria Carina, Daniele Bellavia, Matteo Bulati, Riccardo Alessandro, Milena Fini, Pier Giulio Conaldi, Gianluca Giavaresi
Přispěvatelé:	Raimondi, Lavinia, Gallo, Alessia, Cuscino, Nicola, De Luca, Angela, Costa, Viviana, Carina, Valeria, Bellavia, Daniele, Bulati, Matteo, Alessandro, Riccardo, Fini, Milena, Conaldi, Pier Giulio, Giavaresi, Gianluca
Rok vydání:	2022
Předmět:	Epithelial-Mesenchymal Transition QH301-705.5 MAP Kinase Signaling System EMT protein Bone Neoplasms Article Catalysis Cell Line Inorganic Chemistry Cell Line Tumor Human Umbilical Vein Endothelial Cells metastasis Humans Neoplasm Invasiveness Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Spectroscopy Osteosarcoma Osteoblasts microRNA Neovascularization Pathologic Organic Chemistry EMT proteins tumor angiogenesis General Medicine microRNAs Computer Science Applications Gene Expression Regulation Neoplastic Chemistry osteosarcoma metastasi tumor angiogenesi
Zdroj:	International Journal of Molecular Sciences International Journal of Molecular Sciences; Volume 23; Issue 2; Pages: 705 International Journal of Molecular Sciences, Vol 23, Iss 705, p 705 (2022)
ISSN:	1422-0067
DOI:	10.3390/ijms23020705
Popis:	Osteosarcoma (OS) is the most common primary bone tumor mainly occurring in young adults and derived from primitive bone-forming mesenchyme. OS develops in an intricate tumor microenvironment (TME) where cellular function regulated by microRNAs (miRNAs) may affect communication between OS cells and the surrounding TME. Therefore, miRNAs are considered potential therapeutic targets in cancer and one of the goals of research is to accurately define a specific signature of a miRNAs, which could reflect the phenotype of a particular tumor, such as OS. Through NGS approach, we previously found a specific molecular profile of miRNAs in OS and discovered 8 novel miRNAs. Among these, we deepen our knowledge on the fifth candidate renamed now miR-CT3. MiR-CT3 expression was low in OS cells when compared with human primary osteoblasts and healthy bone. Through TargetScan, VEGF-A was predicted as a potential biological target of miR-CT3 and luciferase assay confirmed it. We showed that enforced expression of miR-CT3 in two OS cell lines, SAOS-2 and MG-63, reduced expression of VEGF-A mRNA and protein, inhibiting tumor angiogenesis. Enforced expression of miR-CT3 also reduced OS cell migration and invasion as confirmed by soft agar colony formation assay. Interestingly, we found that miR-CT3 behaves inducing the activation of p38 MAP kinase pathway and modulating the epithelial-mesenchymal transition (EMT) proteins, in particular reducing Vimentin expression. Overall, our study highlights the novel role of miR-CT3 in regulating tumor angiogenesis and progression in OS cells, linking also to the modulation of EMT proteins.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e1c9bc5924d17a6cdf3c9daecbbc699 https://doi.org/10.3390/ijms23020705 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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