Engineered exosome-mediated delivery of circDIDO1 inhibits gastric cancer progression via regulation of MiR-1307-3p/SOCS2 Axis
Abstract 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 circDIDO...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03527-z |
| _version_ | 1811287422650023936 |
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| author | Zhen Guo Yu Zhang Wenrong Xu Xu Zhang Jiajia Jiang |
| author_facet | Zhen Guo Yu Zhang Wenrong Xu Xu Zhang Jiajia Jiang |
| author_sort | Zhen Guo |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T03:18:10Z |
| format | Article |
| id | doaj.art-197535dafb3541ca9246f84f6babdef9 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-13T03:18:10Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-197535dafb3541ca9246f84f6babdef92022-12-22T03:04:50ZengBMCJournal of Translational Medicine1479-58762022-07-0120111510.1186/s12967-022-03527-zEngineered exosome-mediated delivery of circDIDO1 inhibits gastric cancer progression via regulation of MiR-1307-3p/SOCS2 AxisZhen Guo0Yu Zhang1Wenrong Xu2Xu Zhang3Jiajia Jiang4Aoyang Institute of Cancer, Affiliated Aoyang Hospital of Jiangsu UniversityAoyang Institute of Cancer, Affiliated Aoyang Hospital of Jiangsu UniversityAoyang Institute of Cancer, Affiliated Aoyang Hospital of Jiangsu UniversityAoyang Institute of Cancer, Affiliated Aoyang Hospital of Jiangsu UniversityAoyang Institute of Cancer, Affiliated Aoyang Hospital of Jiangsu UniversityAbstract 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.https://doi.org/10.1186/s12967-022-03527-zGastric cancerCirDIDO1MiR-1307-3pSOCS2ExosomesCancer therapy |
| spellingShingle | Zhen Guo Yu Zhang Wenrong Xu Xu Zhang Jiajia Jiang Engineered exosome-mediated delivery of circDIDO1 inhibits gastric cancer progression via regulation of MiR-1307-3p/SOCS2 Axis Journal of Translational Medicine Gastric cancer CirDIDO1 MiR-1307-3p SOCS2 Exosomes Cancer therapy |
| title | Engineered exosome-mediated delivery of circDIDO1 inhibits gastric cancer progression via regulation of MiR-1307-3p/SOCS2 Axis |
| title_full | Engineered exosome-mediated delivery of circDIDO1 inhibits gastric cancer progression via regulation of MiR-1307-3p/SOCS2 Axis |
| title_fullStr | Engineered exosome-mediated delivery of circDIDO1 inhibits gastric cancer progression via regulation of MiR-1307-3p/SOCS2 Axis |
| title_full_unstemmed | Engineered exosome-mediated delivery of circDIDO1 inhibits gastric cancer progression via regulation of MiR-1307-3p/SOCS2 Axis |
| title_short | Engineered exosome-mediated delivery of circDIDO1 inhibits gastric cancer progression via regulation of MiR-1307-3p/SOCS2 Axis |
| title_sort | engineered exosome mediated delivery of circdido1 inhibits gastric cancer progression via regulation of mir 1307 3p socs2 axis |
| topic | Gastric cancer CirDIDO1 MiR-1307-3p SOCS2 Exosomes Cancer therapy |
| url | https://doi.org/10.1186/s12967-022-03527-z |
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