circPVT1 Facilitates Invasion and Metastasis by Regulating miR-205-5p/c-FLIP Axis in Osteosarcoma
Yu-Peng Liu, Jun Wan, Feng Long, Jian Tian, Can Zhang Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, People’s Republic of ChinaCorrespondence: Can ZhangDepartment of Orthopaedics, Xiangya Hospital, Central South University, No. 87,...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2020-02-01
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| Series: | Cancer Management and Research |
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| Online Access: | https://www.dovepress.com/circpvt1-facilitates-invasion-and-metastasis-by-regulating-mir-205-5pc-peer-reviewed-article-CMAR |
| _version_ | 1818997111400693760 |
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| author | Liu YP Wan J Long F Tian J Zhang C |
| author_facet | Liu YP Wan J Long F Tian J Zhang C |
| author_sort | Liu YP |
| collection | DOAJ |
| description | Yu-Peng Liu, Jun Wan, Feng Long, Jian Tian, Can Zhang Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, People’s Republic of ChinaCorrespondence: Can ZhangDepartment of Orthopaedics, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha 410008, Hunan Province, People’s Republic of ChinaTel +86-138 0841 4883Email zhangcan007@csu.edu.cnBackground: As a key subtype of non-coding RNAs, circular RNA (circRNA) has been well documented to play a key role in the tumorigenesis of osteosarcoma (OS). circPVT1 was revealed to participate in the progression of multiple human tumors; however, the roles of circPVT1 in OS invasion and metastasis and its potential mechanisms remain elusive.Methods: RNA expression in OS tissues and cells was examined by qRT-PCR, protein expression was measured by Western blot. circPVT1 knockdown in vitro was achieved by transfecting OS cells with specific siRNAs. OS cell proliferation was assessed via CCK-8 and colony formation assays. OS cell migration and invasion were evaluated by transwell assay. Interaction between miR-205-5p and circPVT1 or c-FLIP was validated through dual-luciferase reporter assay. Rescue experiments were performed to explore the regulatory net among circPVT1, miR-205-5p and c-FLIP in OS progression in vitro.Results: circPVT1 and c-FLIP were highly expressed, while miR-205-5p was lowly expressed in OS tissues and cell lines. Knockdown of circPVT1 repressed cell proliferation, migration and invasion via inhibiting epithelial–mesenchymal transition (EMT) in OS. circPVT1 functioned as a sponge of miR-205-5p, and c-FLIP was targeted by miR-205-5p in OS cells. Furthermore, circPVT1 indirectly regulated c-FLIP expression through competitively binding to miR-205-5p. Inhibition of miR-205-5p or overexpression of c-FLIP abolished the effects of si-circPVT1 on cell proliferation, migration and invasion.Conclusion: Our study demonstrated circPVT1 functions as a sponge for miR-205-5p to promote c-FLIP expression, thereby enhancing EMT and inducing OS invasion and metastasis in vitro, implying that circPVT1 might be a potential therapeutic target for further clinical therapy of OS.Keywords: osteosarcoma, circPVT1, miR-205-5p, c-FLIP, invasion and metastasis |
| first_indexed | 2024-12-20T21:40:26Z |
| format | Article |
| id | doaj.art-a2b136c45d6e447587b7f411f00af9a5 |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-20T21:40:26Z |
| publishDate | 2020-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-a2b136c45d6e447587b7f411f00af9a52022-12-21T19:25:50ZengDove Medical PressCancer Management and Research1179-13222020-02-01Volume 121229124051903circPVT1 Facilitates Invasion and Metastasis by Regulating miR-205-5p/c-FLIP Axis in OsteosarcomaLiu YPWan JLong FTian JZhang CYu-Peng Liu, Jun Wan, Feng Long, Jian Tian, Can Zhang Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, People’s Republic of ChinaCorrespondence: Can ZhangDepartment of Orthopaedics, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha 410008, Hunan Province, People’s Republic of ChinaTel +86-138 0841 4883Email zhangcan007@csu.edu.cnBackground: As a key subtype of non-coding RNAs, circular RNA (circRNA) has been well documented to play a key role in the tumorigenesis of osteosarcoma (OS). circPVT1 was revealed to participate in the progression of multiple human tumors; however, the roles of circPVT1 in OS invasion and metastasis and its potential mechanisms remain elusive.Methods: RNA expression in OS tissues and cells was examined by qRT-PCR, protein expression was measured by Western blot. circPVT1 knockdown in vitro was achieved by transfecting OS cells with specific siRNAs. OS cell proliferation was assessed via CCK-8 and colony formation assays. OS cell migration and invasion were evaluated by transwell assay. Interaction between miR-205-5p and circPVT1 or c-FLIP was validated through dual-luciferase reporter assay. Rescue experiments were performed to explore the regulatory net among circPVT1, miR-205-5p and c-FLIP in OS progression in vitro.Results: circPVT1 and c-FLIP were highly expressed, while miR-205-5p was lowly expressed in OS tissues and cell lines. Knockdown of circPVT1 repressed cell proliferation, migration and invasion via inhibiting epithelial–mesenchymal transition (EMT) in OS. circPVT1 functioned as a sponge of miR-205-5p, and c-FLIP was targeted by miR-205-5p in OS cells. Furthermore, circPVT1 indirectly regulated c-FLIP expression through competitively binding to miR-205-5p. Inhibition of miR-205-5p or overexpression of c-FLIP abolished the effects of si-circPVT1 on cell proliferation, migration and invasion.Conclusion: Our study demonstrated circPVT1 functions as a sponge for miR-205-5p to promote c-FLIP expression, thereby enhancing EMT and inducing OS invasion and metastasis in vitro, implying that circPVT1 might be a potential therapeutic target for further clinical therapy of OS.Keywords: osteosarcoma, circPVT1, miR-205-5p, c-FLIP, invasion and metastasishttps://www.dovepress.com/circpvt1-facilitates-invasion-and-metastasis-by-regulating-mir-205-5pc-peer-reviewed-article-CMARosteosarcomacircpvt1mir-205-5pc-flipinvasion and metastasis |
| spellingShingle | Liu YP Wan J Long F Tian J Zhang C circPVT1 Facilitates Invasion and Metastasis by Regulating miR-205-5p/c-FLIP Axis in Osteosarcoma Cancer Management and Research osteosarcoma circpvt1 mir-205-5p c-flip invasion and metastasis |
| title | circPVT1 Facilitates Invasion and Metastasis by Regulating miR-205-5p/c-FLIP Axis in Osteosarcoma |
| title_full | circPVT1 Facilitates Invasion and Metastasis by Regulating miR-205-5p/c-FLIP Axis in Osteosarcoma |
| title_fullStr | circPVT1 Facilitates Invasion and Metastasis by Regulating miR-205-5p/c-FLIP Axis in Osteosarcoma |
| title_full_unstemmed | circPVT1 Facilitates Invasion and Metastasis by Regulating miR-205-5p/c-FLIP Axis in Osteosarcoma |
| title_short | circPVT1 Facilitates Invasion and Metastasis by Regulating miR-205-5p/c-FLIP Axis in Osteosarcoma |
| title_sort | circpvt1 facilitates invasion and metastasis by regulating mir 205 5p c flip axis in osteosarcoma |
| topic | osteosarcoma circpvt1 mir-205-5p c-flip invasion and metastasis |
| url | https://www.dovepress.com/circpvt1-facilitates-invasion-and-metastasis-by-regulating-mir-205-5pc-peer-reviewed-article-CMAR |
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