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Synthetic circular miR-21 RNA decoys enhance tumor suppressor expression and impair tumor growth in mice (small RNA-Seq II)

ABSTRACT: Synthetic circular miR-21 RNA decoys enhance tumor suppressor expression and impair tumor growth in mice (small RNA-Seq II)

PROVIDER: PRJNA625529 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11550217.fastq.gz	Fastqsanger.gz
	SRR11550218.fastq.gz	Fastqsanger.gz
	SRR11550219.fastq.gz	Fastqsanger.gz

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Synthetic circular miR-21 RNA decoys enhance tumor suppressor expression and impair tumor growth in mice (RNA-Seq)

Project description:Natural and synthetic circular RNAs effectively impair miRNA function. MiR-21-5p is a potent oncomiR presenting ~33% of all miRNAs across cancers, ~41% in lung adenocarcinoma (LUAD), and ~68% in LUAD-derived cells. We validate and identify five main tumor suppressors targeted by miR-21-5p by deletion of the MIR21 locus in LUAD cells. Synthetic, liposome-delivered circular miR-21-5p decoys enhance expression of these tumor suppressors and severely impair tumor cell vitality at low doses. Decoy efficacy is not increased by bulging of miR-21-5p targeting sites, but associated with substantial cellular decoy stability, indicated by a half-life of ~20h. The intraperitoneal application of nanoparticle-delivered miR-21-5p decoys significantly impairs tumor growth in mouse LUAD tumor models. Decoys are well tolerated and were enriched in lung tissue. However, despite low decoy abundance, tumor suppressor expression was only increased in subcutaneous tumors. These findings suggest nanoparticle-delivered circular miRNA decoys as potent therapeutics in cancer treatment.

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Synthetic circular miR-21 RNA decoys enhance tumor suppressor expression and impair tumor growth in mice (small RNA-Seq I)

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Synthetic circular miR-21 RNA decoys enhance tumor suppressor expression and impair tumor growth in mice

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Synthetic circular miR-21 RNA decoys enhance tumor suppressor expression and impair tumor growth in mice.

Project description:Naturally occurring circular RNAs efficiently impair miRNA functions. Synthetic circular RNAs may thus serve as potent agents for miRNA inhibition. Their therapeutic effect critically relies on (i) the identification of optimal miRNA targets, (ii) the optimization of decoy structures and (iii) the development of efficient formulations for their use as drugs. In this study, we extensively explored the functional relevance of miR-21-5p in cancer cells. Analyses of cancer transcriptomes reveal that miR-21-5p is the by far most abundant miRNA in human cancers. Deletion of the MIR21 locus in cancer-derived cells identifies several direct and indirect miR-21-5p targets, including major tumor suppressors with prognostic value across cancers. To impair miR-21-5p activities, we evaluate synthetic, circular RNA decoys containing four repetitive binding elements. In cancer cells, these decoys efficiently elevate tumor suppressor expression and impair tumor cell vitality. For their in vivo delivery, we for the first time evaluate the formulation of decoys in polyethylenimine (PEI)-based nanoparticles. We demonstrate that PEI/decoy nanoparticles lead to a significant inhibition of tumor growth in a lung adenocarcinoma xenograft mouse model via the upregulation of tumor suppressor expression. These findings introduce nanoparticle-delivered circular miRNA decoys as a powerful potential therapeutic strategy in cancer treatment.

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Lipids impair NK cell anti-tumor immunity and transcription [RNA-seq]

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