Dataset Information

LncRNA MALAT1 Promotes Tumor Angiogenesis by Regulating MicroRNA-150-5p/VEGFA Signaling in Osteosarcoma: In-Vitro and In-Vivo Analyses.

ABSTRACT: The present study aims to analyze the expression of long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in human osteosarcoma (OS) cells and to investigate its role in OS-induced angiogenesis. MALAT1 expression in OS cells was significantly higher than in normal osteoblasts. The functional analysis indicated that MALAT1 appears to enhance OS-induced angiogenesis, in vitro and in vivo analyses, endothelial cell proliferation and migration, chick embryo angiogenesis assay, and zebrafish xenograft model. Mechanistically, silencing MALAT1 downregulated vascular endothelial growth factor A (VEGFA) expression and upregulated miR-150-5p expression in OS cells, and MALAT1-mediated angiogenic induction by VEGFA in OS microenvironment. Moreover, MALAT1 directly targeted miR-150-5p and miR-150-5p directly target VEGFA in OS. Overexpression of miR-150-5p downregulates VEGFA expression in OS. More notably, we showed that MALAT1 induced angiogenesis in OS microenvironment by upregulating the expression of VEGFA via targeting miR-150-5p. Overall, our findings suggest that MALAT1 promotes angiogenesis by regulating the miR-150-5p/VEGFA signaling in OS microenvironment. The findings of the molecular mechanisms of MALAT1 in tumor angiogenesis offer a new viewpoint on OS treatment.

SUBMITTER: Vimalraj S

PROVIDER: S-EPMC8529043 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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LncRNA MALAT1 Promotes Tumor Angiogenesis by Regulating MicroRNA-150-5p/VEGFA Signaling in Osteosarcoma: In-Vitro and In-Vivo Analyses.

Vimalraj Selvaraj S Subramanian Raghunandhakumar R Dhanasekaran Anuradha A

Frontiers in oncology 20211007

The present study aims to analyze the expression of long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in human osteosarcoma (OS) cells and to investigate its role in OS-induced angiogenesis. MALAT1 expression in OS cells was significantly higher than in normal osteoblasts. The functional analysis indicated that MALAT1 appears to enhance OS-induced angiogenesis, in vitro and in vivo analyses, endothelial cell proliferation and migration, chi ...[more]

PMID: 34692524

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Project description:BackgroundOsteosarcoma (OS) is the most common primary bone malignancy in children and adolescents. microRNAs have been found to play a vital role in tumor angiogenesis. Here, we investigated the effects of miR-199a-5p on tumor growth and angiogenesis in osteosarcoma. Furthermore, the underlying molecular mechanisms and signaling pathways were explored.MethodsThe datasets were extracted from the Gene Expression Omnibus and the differentially expressed miRNAs (DEmiRNAs) were screened out by the GEO2R online platform. The potential target genes were predicted using the miRTarBase database. The predicted target genes were further analyzed by Gene Ontology and pathway enrichment analysis and a regulatory network of DEmiRNAs and their target genes was constructed. In addition, the effects of osteosarcoma cell derived exosomal miR-199a-5p on the proliferation, migration and neovascularization of HUVECs were evaluated by conducting EdU assays, Transwell experiments and tube formation assays. A dual-luciferase reporter assay was performed to detect whether VEGFA was the direct target of miR-199a-5p. Furthermore, in vivo xenograft models were established to further investigate the intrinsic role of miR-199a-5p in osteosarcoma tumorigenesis and angiogenesis.ResultsA total of 149 DE-miRNAs were screened out, including 136 upregulated miRNAs and 13 downregulated miRNAs in human osteosarcoma plasma samples compared with normal plasma samples. A total of 1313 target genes of the top three upregulated and downregulated miRNAs were predicted. In the PPI network, the top 10 hub nodes with higher degrees were identified as hub genes, such as TP53 and VEGFA. By constructing the miRNA-hub gene network, we found that most of hub genes could be potentially modulated by miR-663a, miR-199a-5p and miR-223-3p. In addition, we found that the expression level of miR-199a-5p in exosomes derived from osteosarcoma cells was remarkably higher than the osteosarcoma cells, and the exosomes derived from osteosarcoma cells were transported to HUVECs. Overexpression of miR-199a-5p could significantly inhibited HUVEC proliferation, migration and neovascularization, whereas downregulation of miR-199a-5p expression exerted the opposite effect. Moreover, the in vivo results verified that overexpression of miR-199a-5p in osteosarcoma cells could suppress the growth and angiogenesis of tumors.ConclusionOur results demonstrated that miR-199a-5p could be transported from osteosarcoma cells to HUVECs through exosomes, subsequently targeting VEGFA and inhibiting the growth and angiogenesis of osteosarcoma. Therefore, miR-199a-5p may act as a biomarker in the diagnosis and treatment of osteosarcoma.

Dataset Information

LncRNA MALAT1 Promotes Tumor Angiogenesis by Regulating MicroRNA-150-5p/VEGFA Signaling in Osteosarcoma: In-Vitro and In-Vivo Analyses.

Publications

LncRNA MALAT1 Promotes Tumor Angiogenesis by Regulating MicroRNA-150-5p/VEGFA Signaling in Osteosarcoma: <i>In-Vitro</i> and <i>In-Vivo</i> Analyses.

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