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Title:
Engineered exosome-mediated delivery of circDIDO1 inhibits gastric cancer progression via regulation of MiR-1307-3p/SOCS2 Axis | Journal of Translational Medicine
Description:
Background Our previous study has identified a novel circRNA (circDIDO1) that is down-regulated in gastric cancer (GC) and significantly inhibits GC progression. The purpose of this study is to identify the molecular mechanism for circDIDO1 and to evaluate the therapeutic effect of circDIDO1 in GC. Methods By combining bioinformatic analysis with RNA sequencing data, we predicted the potential target of circDIDO1 and further validated the regulatory mechanisms for its tumor suppressor function in GC. RIP assay, luciferase reporter assay and in vitro cell function assays were performed to analyze circDIDO1-regulated downstream target genes. For the therapeutic study, circDIDO1-loaded, RGD-modified exosomes (RGD-Exo-circDIDO1) were constructed and its anti-tumor efficacy and biological safety were evaluated in vitro and in vivo. Results CircDIDO1 inhibited GC progression by regulating the expression of the signal transducer inhibitor SOSC2 through sponging miR-1307-3p. Overexpression of circDIDO1 or SOSC2 antagonized the oncogenic role of miR-1307-3p. RGD-Exo-circDIDO1 could efficiently deliver circDIDO1 to increase SOCS2 expression in GC cells. Compared with PBS and RGD-Exo-vector treatment, RGD-Exo-circDIDO1 treatment significantly inhibited the proliferation, migration and invasion of GC cells while promoted cell apoptosis. The therapeutic efficacy of RGD-Exo-circDIDO1 was further confirmed in a mouse xenograft tumor model. In addition, major tissues including the heart, liver, spleen, lungs and kidneys showed no obvious histopathological abnormalities or lesions in the RGD-Exo-circDIDO1 treated group. Conclusion Our findings revealed that circDIDO1 suppressed the progression of GC via modulating the miR-1307-3p/SOSC2 axis. Systemic administration of RGD modified, circDIDO1 loaded exosomes repressed the tumorigenicity and aggressiveness of GC both in vitro and in vivo, suggesting that RGD-Exo-circDIDO1 could be used as a feasible nanomedicine for GC therapy.
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Keywords {🔍}
circdido, pubmed, cancer, cells, article, mirp, google, scholar, exosomes, rgdexocircdido, cas, cell, socs, fig, progression, expression, rna, wang, data, zhang, delivery, gastric, tumor, tissues, central, analysis, results, treatment, effect, invasion, treated, circular, therapeutic, assay, shown, function, axis, study, luciferase, engineered, inhibits, reporter, migration, protein, usa, growth, vivo, pbs, significant, mice,
Topics {✒️}
targeting mir-203a-3p/socs3 axis circdido1/mir-1307-3p/socs2 signaling pathway mir-141-3p/pten/akt pathway triple-negative breast cancer including mir-196a/mir-196b [36] regulate socs2/jak/stat signaling mir-1307-3p/socs2 axis plays dendritic cell-derived exosomes wnt2/β-catenin pathway [31] dii-labeled rgd-exo-circdido1 scale bars = 100 μm scale bars = 60 μm rgd-exo-circdido1 treated group rgd-exo-circdido1 treatment led wnt2/beta-catenin pathway microrna-196a/-196b regulate article download pdf anti-cancer drug 5-fu relieving beta-cell destruction vivo β-catenin attenuation msc-derived exosomes loaded cell-penetrating inhibitory peptides mir-1307-3p/smg1 axis [33] mir-1307-3p/smg1 axis exosome-based rna delivery nano-scale size engineered exosome-based delivery rna-induced silencing complex engineered exosome-mediated delivery circdido1/mir-1307-3p axis mir-1307-3p/sosc2 axis mir-1307-3p/socs2 axis form rgd-exo-vector cytokine-induced signaling transduction extracellular membrane-derived vesicles extracellular vesicle-mediated delivery nf-κb regulator encoded facilitating hur-repressed functions rgd-exo-circdido1 ranged scale bar = 20 μm exosome-based circrna delivery rgd-exo-vector treatment reduce mir-142-3p levels human bladder cancer efficient anti-tumor effect rgd-exo-circdido1 treatment tissue-specific expression patterns rgd-engineered exosomes labeling ki-67-positive proliferating cells tunel-positive apoptotic cells
Questions {❓}
- Is gastric cancer preventable?
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headline:Engineered exosome-mediated delivery of circDIDO1 inhibits gastric cancer progression via regulation of MiR-1307-3p/SOCS2 Axis
description:Our previous study has identified a novel circRNA (circDIDO1) that is down-regulated in gastric cancer (GC) and significantly inhibits GC progression. The purpose of this study is to identify the molecular mechanism for circDIDO1 and to evaluate the therapeutic effect of circDIDO1 in GC. By combining bioinformatic analysis with RNA sequencing data, we predicted the potential target of circDIDO1 and further validated the regulatory mechanisms for its tumor suppressor function in GC. RIP assay, luciferase reporter assay and in vitro cell function assays were performed to analyze circDIDO1-regulated downstream target genes. For the therapeutic study, circDIDO1-loaded, RGD-modified exosomes (RGD-Exo-circDIDO1) were constructed and its anti-tumor efficacy and biological safety were evaluated in vitro and in vivo. CircDIDO1 inhibited GC progression by regulating the expression of the signal transducer inhibitor SOSC2 through sponging miR-1307-3p. Overexpression of circDIDO1 or SOSC2 antagonized the oncogenic role of miR-1307-3p. RGD-Exo-circDIDO1 could efficiently deliver circDIDO1 to increase SOCS2 expression in GC cells. Compared with PBS and RGD-Exo-vector treatment, RGD-Exo-circDIDO1 treatment significantly inhibited the proliferation, migration and invasion of GC cells while promoted cell apoptosis. The therapeutic efficacy of RGD-Exo-circDIDO1 was further confirmed in a mouse xenograft tumor model. In addition, major tissues including the heart, liver, spleen, lungs and kidneys showed no obvious histopathological abnormalities or lesions in the RGD-Exo-circDIDO1 treated group. Our findings revealed that circDIDO1 suppressed the progression of GC via modulating the miR-1307-3p/SOSC2 axis. Systemic administration of RGD modified, circDIDO1 loaded exosomes repressed the tumorigenicity and aggressiveness of GC both in vitro and in vivo, suggesting that RGD-Exo-circDIDO1 could be used as a feasible nanomedicine for GC therapy.
datePublished:2022-07-21T00:00:00Z
dateModified:2022-07-21T00:00:00Z
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Gastric cancer
CirDIDO1
MiR-1307-3p
SOCS2
Exosomes
Cancer therapy
Biomedicine
general
Medicine/Public Health
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headline:Engineered exosome-mediated delivery of circDIDO1 inhibits gastric cancer progression via regulation of MiR-1307-3p/SOCS2 Axis
description:Our previous study has identified a novel circRNA (circDIDO1) that is down-regulated in gastric cancer (GC) and significantly inhibits GC progression. The purpose of this study is to identify the molecular mechanism for circDIDO1 and to evaluate the therapeutic effect of circDIDO1 in GC. By combining bioinformatic analysis with RNA sequencing data, we predicted the potential target of circDIDO1 and further validated the regulatory mechanisms for its tumor suppressor function in GC. RIP assay, luciferase reporter assay and in vitro cell function assays were performed to analyze circDIDO1-regulated downstream target genes. For the therapeutic study, circDIDO1-loaded, RGD-modified exosomes (RGD-Exo-circDIDO1) were constructed and its anti-tumor efficacy and biological safety were evaluated in vitro and in vivo. CircDIDO1 inhibited GC progression by regulating the expression of the signal transducer inhibitor SOSC2 through sponging miR-1307-3p. Overexpression of circDIDO1 or SOSC2 antagonized the oncogenic role of miR-1307-3p. RGD-Exo-circDIDO1 could efficiently deliver circDIDO1 to increase SOCS2 expression in GC cells. Compared with PBS and RGD-Exo-vector treatment, RGD-Exo-circDIDO1 treatment significantly inhibited the proliferation, migration and invasion of GC cells while promoted cell apoptosis. The therapeutic efficacy of RGD-Exo-circDIDO1 was further confirmed in a mouse xenograft tumor model. In addition, major tissues including the heart, liver, spleen, lungs and kidneys showed no obvious histopathological abnormalities or lesions in the RGD-Exo-circDIDO1 treated group. Our findings revealed that circDIDO1 suppressed the progression of GC via modulating the miR-1307-3p/SOSC2 axis. Systemic administration of RGD modified, circDIDO1 loaded exosomes repressed the tumorigenicity and aggressiveness of GC both in vitro and in vivo, suggesting that RGD-Exo-circDIDO1 could be used as a feasible nanomedicine for GC therapy.
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Gastric cancer
CirDIDO1
MiR-1307-3p
SOCS2
Exosomes
Cancer therapy
Biomedicine
general
Medicine/Public Health
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