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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: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE148735 | GEO | 2020/07/20

REPOSITORIES: GEO

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

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.

2020-07-20 | GSE148734 | GEO

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

2020-07-20 | GSE148684 | GEO

Global characterization of miR-574-5p decoy to CUGBP1 in human lung cancer using a mass spectrometry proteomics approach

Project description:We aimed to characterize decoy to the RNA-binding protein CUG-RNA binding protein 1 (CUGBP1 mechanism in A549 lung cancer cells. We identified several new canonical targets of CUGBP1 but those were not regulated by miR-574-5p via the decoy mechanism. This can be explained by the localization of CUGBP1 and miR-574-5p in the nucleus, where CUGBP1 regulates alternative splicing. Next, we analyzed the 3’UTRs of potential targets and found that the decoy-dependent regulation of mPGES-1 splicing is unique. Therefore, we postulate that in A549 cells mPGES-1 is the only protein regulated by the decoy mechanism of CUGBP1 and miR-574-5p which suggests that the decoy mechanism allows the specific regulation of the expression of distinct targets.

2020-03-02 | PXD016803 | Pride

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

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

| PRJNA625524 | ENA

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

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

| PRJNA625337 | ENA

What goes around comes around: artificial circular RNAs bypass cellular antiviral responses

Project description:Natural circular RNAs have been found to sequester microRNAs and suppress their function. We have used this principle as a molecular tool, and produced artificial circular RNA sponges in a cell-free system by in vitro transcription and ligation. Formerly, we were able to inhibit hepatitis C virus propagation by applying a circular RNA decoy strategy against microRNA-122, which is essential for the viral life cycle. In another proof-of-principle study, we used circular RNAs to sequester microRNA-21, an oncogenic and pro-proliferative microRNA. This strategy slowed tumor growth in a 3D cell culture model system, as well as in xenograft mice upon systemic delivery. In the wake of the global use of an in vitro transcribed RNA in Covid-19 vaccines, the question arose if therapeutic circular RNAs trigger cellular antiviral defense mechanisms when delivered systemically. In this study, we present data on the cellular innate immune response as a consequence of liposome-based transfection of the circular RNA sponges we previously used to inhibit microRNA function. We find that circular RNAs produced by the presented methodology do not trigger the antiviral response and do not activate innate immune signaling pathways.

2022-04-08 | GSE192656 | GEO

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

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

| PRJNA625521 | ENA

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

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

| PRJNA625529 | ENA

LncRNA RP3-340N1.2 affects the progression of lung adenocarcinoma cell lines by targeting miR-134-5p

Project description:We found lncRNA RP3-340N1.2 is highly expressed in LUAD and relatived with the progression of LUAD through high-throughput sequencing. Our results showed that the expression level of RP3-340N1.2 was upregulated significantly in three LUAD cell lines (A549, NCI_x001E_H1299, and NCI-H1975) and lentivirus-mediated knockdown of RP3-340N1.2 inhibited the differentiation, proliferation, migration, invasion, cell cycle, and other biological processes of tumor cells significantly. Bioinformatic software predicted the downstream target of RP3-340N1.2, which was verified using dual luciferase assays and other methods. We found that RP3-340N1.2 can competitively bind miR-134-5p in LUAD, and this microRNA has a significant regulatory effect on the expression of epidermal growth factor receptor (EGFR), which leads to increased migration and invasion of LUAD cells. This discovery provided a possible mechanism by which RP3-340N1.2 participates in the development of LUAD. In conclusion, our results showed that lncRNA RP3_x001E_340N1.2 regulates the expression of EGFR indirectly by targeting miR-134-5p and promotes the progression of LUAD. Therefore, RP3-340N1.2 may become a valuable biomarker and therapeutic target in LUAD.

2023-12-01 | GSE190461 | GEO

sRSM1 synthetic decoy vs. scrambled transfections in MDA-MB-231 cells

Project description:Transcriptional profiling of MDA-MB-231 comparing the regulatory consequences of transfecting synthetic decoys carring sRSM1 motifs versus synthetic scrambled oligos Two decoy/scrambled sets, each with two biological replicates

2012-02-28 | E-GEOD-35749 | biostudies-arrayexpress

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