Xiaoping Chen, Xinping Ren, Jiaoting E, Yaqi Zhou, Rongfang Bian
{"title":"外泌体传递的circIFNGR2通过miR-378/ST5轴调节卵巢癌转移","authors":"Xiaoping Chen, Xinping Ren, Jiaoting E, Yaqi Zhou, Rongfang Bian","doi":"10.1080/10985549.2022.2160605","DOIUrl":null,"url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs)-derived exosomes have emerged as a key driver of ovarian cancer (OVCA) tumor progression. The mechanisms behind the specific circular RNA (circRNA) activity encapsulated by CAF-generated exosomes (CAF-exo) requires to be elucidated. Herein, this study selected specific circRNA (hsa_circ<i>IFNGR2</i>) molecules and aimed to clarify novel function of CAF-derived exosomal circ<i>IFNGR2</i> on growth, and metastasis of OVCA cells. In this study, we clarified that the exosomes of CAFs originating from human ovarian cancer hindered tumor cell proliferation, metastasis and EMT in vitro. Interestingly, CAFs directly transferred exosomes into OVCA cells to enrich intracellular circ<i>IFNGR2</i> levels. Biologically, activation of exosomal circ<i>IFNGR2</i> blocked cell proliferation, metastasis and EMT. Mechanistically, enhanced circ<i>IFNGR2</i> activated the miR-378/ST5 axis and directly inhibited the malignant evolution of tumor cells. Furthermore, rescue experiments evidenced that circ<i>IFNGR2</i> and ST5 were two essential participants in OVCA, concretely manifested in the co-culture of OVCA cells with exosomes that reversed the effects of intracellular circ<i>IFNGR2</i> and ST5 depletion. Finally, we observed that CAF-exo treatment hindered tumor growth and increased the size and number of metastatic nodules in mice. Our study revealed a previously unknown regulatory pathway whereby CAFs-derived exosomes delivered circ<i>IFNGR2</i> and inhibited the malignant progression of OVCA by circ<i>IFNGR2</i>/miR-378/ST5 axis.</p>","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"43 1","pages":"22-42"},"PeriodicalIF":3.2000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9937009/pdf/","citationCount":"0","resultStr":"{\"title\":\"Exosome-transmitted circ<i>IFNGR2</i> Modulates Ovarian Cancer Metastasis via miR-378/ST5 Axis.\",\"authors\":\"Xiaoping Chen, Xinping Ren, Jiaoting E, Yaqi Zhou, Rongfang Bian\",\"doi\":\"10.1080/10985549.2022.2160605\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cancer-associated fibroblasts (CAFs)-derived exosomes have emerged as a key driver of ovarian cancer (OVCA) tumor progression. The mechanisms behind the specific circular RNA (circRNA) activity encapsulated by CAF-generated exosomes (CAF-exo) requires to be elucidated. Herein, this study selected specific circRNA (hsa_circ<i>IFNGR2</i>) molecules and aimed to clarify novel function of CAF-derived exosomal circ<i>IFNGR2</i> on growth, and metastasis of OVCA cells. In this study, we clarified that the exosomes of CAFs originating from human ovarian cancer hindered tumor cell proliferation, metastasis and EMT in vitro. Interestingly, CAFs directly transferred exosomes into OVCA cells to enrich intracellular circ<i>IFNGR2</i> levels. Biologically, activation of exosomal circ<i>IFNGR2</i> blocked cell proliferation, metastasis and EMT. Mechanistically, enhanced circ<i>IFNGR2</i> activated the miR-378/ST5 axis and directly inhibited the malignant evolution of tumor cells. Furthermore, rescue experiments evidenced that circ<i>IFNGR2</i> and ST5 were two essential participants in OVCA, concretely manifested in the co-culture of OVCA cells with exosomes that reversed the effects of intracellular circ<i>IFNGR2</i> and ST5 depletion. Finally, we observed that CAF-exo treatment hindered tumor growth and increased the size and number of metastatic nodules in mice. Our study revealed a previously unknown regulatory pathway whereby CAFs-derived exosomes delivered circ<i>IFNGR2</i> and inhibited the malignant progression of OVCA by circ<i>IFNGR2</i>/miR-378/ST5 axis.</p>\",\"PeriodicalId\":18658,\"journal\":{\"name\":\"Molecular and Cellular Biology\",\"volume\":\"43 1\",\"pages\":\"22-42\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9937009/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular and Cellular Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/10985549.2022.2160605\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/1/26 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/10985549.2022.2160605","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/26 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Exosome-transmitted circIFNGR2 Modulates Ovarian Cancer Metastasis via miR-378/ST5 Axis.
Cancer-associated fibroblasts (CAFs)-derived exosomes have emerged as a key driver of ovarian cancer (OVCA) tumor progression. The mechanisms behind the specific circular RNA (circRNA) activity encapsulated by CAF-generated exosomes (CAF-exo) requires to be elucidated. Herein, this study selected specific circRNA (hsa_circIFNGR2) molecules and aimed to clarify novel function of CAF-derived exosomal circIFNGR2 on growth, and metastasis of OVCA cells. In this study, we clarified that the exosomes of CAFs originating from human ovarian cancer hindered tumor cell proliferation, metastasis and EMT in vitro. Interestingly, CAFs directly transferred exosomes into OVCA cells to enrich intracellular circIFNGR2 levels. Biologically, activation of exosomal circIFNGR2 blocked cell proliferation, metastasis and EMT. Mechanistically, enhanced circIFNGR2 activated the miR-378/ST5 axis and directly inhibited the malignant evolution of tumor cells. Furthermore, rescue experiments evidenced that circIFNGR2 and ST5 were two essential participants in OVCA, concretely manifested in the co-culture of OVCA cells with exosomes that reversed the effects of intracellular circIFNGR2 and ST5 depletion. Finally, we observed that CAF-exo treatment hindered tumor growth and increased the size and number of metastatic nodules in mice. Our study revealed a previously unknown regulatory pathway whereby CAFs-derived exosomes delivered circIFNGR2 and inhibited the malignant progression of OVCA by circIFNGR2/miR-378/ST5 axis.
期刊介绍:
Molecular and Cellular Biology (MCB) showcases significant discoveries in cellular morphology and function, genome organization, regulation of genetic expression, morphogenesis, and somatic cell genetics. The journal also examines viral systems, publishing papers that emphasize their impact on the cell.