Target gene regulatory network of miR-497 in angiosarcoma.

Autor:	Benton A; Department of Biological Sciences, Purdue University, West Lafayette, IN USA.; Purdue University Institute for Cancer Research, Purdue University, West Lafayette, IN USA., Terwilliger E; Department of Biological Sciences, Purdue University, West Lafayette, IN USA.; Purdue University Institute for Cancer Research, Purdue University, West Lafayette, IN USA., Moriarty NM; Purdue University Institute for Cancer Research, Purdue University, West Lafayette, IN USA.; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN USA., Liu B; Department of Biological Sciences, Purdue University, West Lafayette, IN USA.; Purdue University Institute for Cancer Research, Purdue University, West Lafayette, IN USA., Murphy A; Department of Biological Sciences, Purdue University, West Lafayette, IN USA.; Purdue University Institute for Cancer Research, Purdue University, West Lafayette, IN USA., Maluvac H; Department of Biological Sciences, Purdue University, West Lafayette, IN USA.; Purdue University Institute for Cancer Research, Purdue University, West Lafayette, IN USA., Shu M; Department of Biological Sciences, Purdue University, West Lafayette, IN USA.; Purdue University Institute for Cancer Research, Purdue University, West Lafayette, IN USA., Gartenhaus LE; Department of Biological Sciences, Purdue University, West Lafayette, IN USA.; Purdue University Institute for Cancer Research, Purdue University, West Lafayette, IN USA., Janson ND; Department of Biological Sciences, Purdue University, West Lafayette, IN USA.; Purdue University Institute for Cancer Research, Purdue University, West Lafayette, IN USA., Pfeffer CM; Department of Biological Sciences, Purdue University, West Lafayette, IN USA.; Purdue University Institute for Cancer Research, Purdue University, West Lafayette, IN USA., Utturkar SM; Purdue University Institute for Cancer Research, Purdue University, West Lafayette, IN USA., Parkinson EI; Purdue University Institute for Cancer Research, Purdue University, West Lafayette, IN USA.; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN USA.; Department of Chemistry, Purdue University, West Lafayette, IN, USA., Lanman NA; Purdue University Institute for Cancer Research, Purdue University, West Lafayette, IN USA.; Department of Comparative Pathobiology, Purdue University, West Lafayette, IN USA., Hanna JA; Department of Biological Sciences, Purdue University, West Lafayette, IN USA.; Purdue University Institute for Cancer Research, Purdue University, West Lafayette, IN USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Sep 25. Date of Electronic Publication: 2023 Sep 25.
DOI:	10.1101/2023.09.24.559218
Abstrakt:	Angiosarcoma (AS) is a vascular sarcoma that is highly aggressive and metastatic. Due to its rarity, treatment options for patients are limited, therefore more research is needed to identify possible therapeutic vulnerabilities. We previously found that conditional deletion of Dicer1 drives AS development in mice. Given the role of DICER1 in canonical microRNA (miRNA) biogenesis, this suggests that miRNA loss is important in AS development. After testing miRNAs previously suggested to have a tumor-suppressive role in AS, microRNA-497-5p (miR-497) suppressed cell viability most significantly. We also found that miR-497 overexpression led to significantly reduced cell migration and tumor formation. To understand the mechanism of miR-497 in tumor suppression, we identified clinically relevant target genes using a combination of RNA-sequencing data in an AS cell line, expression data from AS patients, and target prediction algorithms. We validated miR-497 direct regulation of CCND2, CDK6, and VAT1. One of these genes, VAT1, is an understudied protein that has been suggested to promote cell migration and metastasis in other cancers. Indeed, we find that pharmacologic inhibition of VAT1 with the natural product Neocarzilin A reduces AS migration. This work provides insight into the mechanisms of miR-497 and its target genes in AS pathogenesis. Competing Interests: Competing Interests No competing interests declared.
Databáze:	MEDLINE
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