MicroRNA-16 suppresses metastasis in an orthotopic, but not autochthonous, mouse model of soft tissue sarcoma
MicroRNAs (miRNAs) can regulate tumor cell invasion and metastasis in a tumor-specific manner. We recently demonstrated that global downregulation of miRNAs after deleting dicer can promote development of distant metastases in a mouse model of primary soft tissue sarcoma (STS). In this study, we ide...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2015-08-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/8/8/867 |
| _version_ | 1828391574951690240 |
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| author | Mohit Sachdeva Melody J. Whitley Jeffrey K. Mito Yan Ma Dina C. Lev Diana M. Cardona David G. Kirsch |
| author_facet | Mohit Sachdeva Melody J. Whitley Jeffrey K. Mito Yan Ma Dina C. Lev Diana M. Cardona David G. Kirsch |
| author_sort | Mohit Sachdeva |
| collection | DOAJ |
| description | MicroRNAs (miRNAs) can regulate tumor cell invasion and metastasis in a tumor-specific manner. We recently demonstrated that global downregulation of miRNAs after deleting dicer can promote development of distant metastases in a mouse model of primary soft tissue sarcoma (STS). In this study, we identified miRNAs that are differentially downregulated in metastatic STS in both human and mouse, and investigated the role of these miRNAs in metastasis. miRNA- TaqMan PCR arrays showed a global downregulation of miRNAs in metastatic human sarcomas. Similar analysis in mouse metastatic sarcomas revealed overlap for several downregulated miRNAs including miR-16, miR-103, miR-146a, miR-223, miR-342 and miR-511. Restoration of these downregulated miRNAs in mouse primary sarcoma cell lines showed that miR-16, but not other downregulated miRNAs, was able to significantly suppress both migration and invasion in vitro, without altering cell proliferation. In addition, orthotopic transplantation of a sarcoma cell line stably expressing miR-16 into the muscle of immunocompromised mice revealed that restoration of miR-16 can significantly decrease lung metastasis in vivo. However, no change in the rate of lung metastasis was observed when miR-16 was deleted in mouse primary sarcomas at sarcoma initiation. Taken together, these results indicate that miR-16 can have metastasis-suppressing properties both in vitro and in vivo. However, the loss-of-function experiments in autochthonous tumors indicate that loss of miR-16 is not sufficient to promote metastasis in vivo. |
| first_indexed | 2024-12-10T07:04:35Z |
| format | Article |
| id | doaj.art-28dd44800ac44f89b5c2912db9e5f7a6 |
| institution | Directory Open Access Journal |
| issn | 1754-8411 1754-8403 |
| language | English |
| last_indexed | 2024-12-10T07:04:35Z |
| publishDate | 2015-08-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-28dd44800ac44f89b5c2912db9e5f7a62022-12-22T01:58:13ZengThe Company of BiologistsDisease Models & Mechanisms1754-84111754-84032015-08-018886787510.1242/dmm.017897017897MicroRNA-16 suppresses metastasis in an orthotopic, but not autochthonous, mouse model of soft tissue sarcomaMohit Sachdeva0Melody J. Whitley1Jeffrey K. Mito2Yan Ma3Dina C. Lev4Diana M. Cardona5David G. Kirsch6 Department of Radiation Oncology, Duke University Medical Center, Durham, NC NC27708, USA Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC 27708, USA Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC 27708, USA Department of Radiation Oncology, Duke University Medical Center, Durham, NC NC27708, USA Department of Cancer Biology, University of Texas, MD Anderson Cancer Center, Houston, TX 77054, USA Department of Pathology, Duke University Medical Center, Durham, NC 27708, USA Department of Radiation Oncology, Duke University Medical Center, Durham, NC NC27708, USA MicroRNAs (miRNAs) can regulate tumor cell invasion and metastasis in a tumor-specific manner. We recently demonstrated that global downregulation of miRNAs after deleting dicer can promote development of distant metastases in a mouse model of primary soft tissue sarcoma (STS). In this study, we identified miRNAs that are differentially downregulated in metastatic STS in both human and mouse, and investigated the role of these miRNAs in metastasis. miRNA- TaqMan PCR arrays showed a global downregulation of miRNAs in metastatic human sarcomas. Similar analysis in mouse metastatic sarcomas revealed overlap for several downregulated miRNAs including miR-16, miR-103, miR-146a, miR-223, miR-342 and miR-511. Restoration of these downregulated miRNAs in mouse primary sarcoma cell lines showed that miR-16, but not other downregulated miRNAs, was able to significantly suppress both migration and invasion in vitro, without altering cell proliferation. In addition, orthotopic transplantation of a sarcoma cell line stably expressing miR-16 into the muscle of immunocompromised mice revealed that restoration of miR-16 can significantly decrease lung metastasis in vivo. However, no change in the rate of lung metastasis was observed when miR-16 was deleted in mouse primary sarcomas at sarcoma initiation. Taken together, these results indicate that miR-16 can have metastasis-suppressing properties both in vitro and in vivo. However, the loss-of-function experiments in autochthonous tumors indicate that loss of miR-16 is not sufficient to promote metastasis in vivo.http://dmm.biologists.org/content/8/8/867Genetic engineeringMouse modelsMetastasisMicroRNASoft tissue sarcoma |
| spellingShingle | Mohit Sachdeva Melody J. Whitley Jeffrey K. Mito Yan Ma Dina C. Lev Diana M. Cardona David G. Kirsch MicroRNA-16 suppresses metastasis in an orthotopic, but not autochthonous, mouse model of soft tissue sarcoma Disease Models & Mechanisms Genetic engineering Mouse models Metastasis MicroRNA Soft tissue sarcoma |
| title | MicroRNA-16 suppresses metastasis in an orthotopic, but not autochthonous, mouse model of soft tissue sarcoma |
| title_full | MicroRNA-16 suppresses metastasis in an orthotopic, but not autochthonous, mouse model of soft tissue sarcoma |
| title_fullStr | MicroRNA-16 suppresses metastasis in an orthotopic, but not autochthonous, mouse model of soft tissue sarcoma |
| title_full_unstemmed | MicroRNA-16 suppresses metastasis in an orthotopic, but not autochthonous, mouse model of soft tissue sarcoma |
| title_short | MicroRNA-16 suppresses metastasis in an orthotopic, but not autochthonous, mouse model of soft tissue sarcoma |
| title_sort | microrna 16 suppresses metastasis in an orthotopic but not autochthonous mouse model of soft tissue sarcoma |
| topic | Genetic engineering Mouse models Metastasis MicroRNA Soft tissue sarcoma |
| url | http://dmm.biologists.org/content/8/8/867 |
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