circPVT1 regulates medullary thyroid cancer growth and metastasis by targeting miR-455-5p to activate CXCL12/CXCR4 signaling
Abstract Background Medullary thyroid cancer (MTC) represents 13.4 % of all thyroid cancers-related deaths. The treatments for MTC are very limited especially for patients with distal metastasis. Therefore, it is critical to understand the mechanisms of MTC to pursue novel therapeutic avenues. Here,...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-05-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-021-01964-0 |
| _version_ | 1797555649748402176 |
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| author | Xun Zheng Shu Rui Xiao-Fei Wang Xiu-He Zou Yan-Ping Gong Zhi-Hui Li |
| author_facet | Xun Zheng Shu Rui Xiao-Fei Wang Xiu-He Zou Yan-Ping Gong Zhi-Hui Li |
| author_sort | Xun Zheng |
| collection | DOAJ |
| description | Abstract Background Medullary thyroid cancer (MTC) represents 13.4 % of all thyroid cancers-related deaths. The treatments for MTC are very limited especially for patients with distal metastasis. Therefore, it is critical to understand the mechanisms of MTC to pursue novel therapeutic avenues. Here, we studied the function of circPVT1/miR-455-5p in MTC. Methods Human MTC tissues and cell lines were used. qRT-PCR and Western blotting were employed to measure expression levels of miR-455-5p, circPVT1, CXCL12, and epithelial mesenchymal transformation (EMT)-related proteins. Colony formation assay, flow cytometry, transwell assay, and scratch wound healing assay were used to assess the abilities of cell proliferation, apoptosis, migration and invasion, respectively. Dual luciferase assay and RNA immunoprecipitation were employed to validate interactions of circPVT1/miR-455-5p and miR-455-5p/CXCL12. Nude mouse xenograft model was used to evaluate the effects of shcircPVT1 and miR-455-5p mimics on tumor growth and metastasis in vivo. Results miR-455-5p was reduced in MTC tissues and cells while circPVT1 was elevated. Their levels were correlated with prognosis of MTC. Overexpression of miR-455-5p or sh-circPVT1 suppressed EMT and MTC cell proliferation, migration and invasion. miR-455-5p targeted CXCL12 while circPVT1 sponged miR-455-5p. Knockdown of CXCL12 or CXCL12/CXCR4 signaling inhibitor reversed the effects of circPVT1 overexpression or miR-455-5p inhibitor on EMT and MTC cell proliferation, migration and invasion. Knockdown of circPVT1 or miR-455-5p overexpression repressed MTC tumor growth and lung metastasis in vivo. Conclusions miR-455-5p suppresses MTC growth and metastasis by targeting CXCL12/CXCR4 signaling pathway while circPVT1 promotes MTC by sponging miR-455-5p. Our study sheds light on the mechanisms of MTC growth and metastasis. |
| first_indexed | 2024-03-10T16:50:30Z |
| format | Article |
| id | doaj.art-2a2ce5419a57491089a86f55fe711337 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-03-10T16:50:30Z |
| publishDate | 2021-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-2a2ce5419a57491089a86f55fe7113372023-11-20T11:18:33ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662021-05-0140111710.1186/s13046-021-01964-0circPVT1 regulates medullary thyroid cancer growth and metastasis by targeting miR-455-5p to activate CXCL12/CXCR4 signalingXun Zheng0Shu Rui1Xiao-Fei Wang2Xiu-He Zou3Yan-Ping Gong4Zhi-Hui Li5Department of Thyroid and Parathyroid Surgery Center, West China Hospital, Sichuan UniversityDepartment of Thyroid and Parathyroid Surgery Center, West China Hospital, Sichuan UniversityDepartment of Thyroid and Parathyroid Surgery Center, West China Hospital, Sichuan UniversityDepartment of Thyroid and Parathyroid Surgery Center, West China Hospital, Sichuan UniversityDepartment of Thyroid and Parathyroid Surgery Center, West China Hospital, Sichuan UniversityDepartment of Thyroid and Parathyroid Surgery Center, West China Hospital, Sichuan UniversityAbstract Background Medullary thyroid cancer (MTC) represents 13.4 % of all thyroid cancers-related deaths. The treatments for MTC are very limited especially for patients with distal metastasis. Therefore, it is critical to understand the mechanisms of MTC to pursue novel therapeutic avenues. Here, we studied the function of circPVT1/miR-455-5p in MTC. Methods Human MTC tissues and cell lines were used. qRT-PCR and Western blotting were employed to measure expression levels of miR-455-5p, circPVT1, CXCL12, and epithelial mesenchymal transformation (EMT)-related proteins. Colony formation assay, flow cytometry, transwell assay, and scratch wound healing assay were used to assess the abilities of cell proliferation, apoptosis, migration and invasion, respectively. Dual luciferase assay and RNA immunoprecipitation were employed to validate interactions of circPVT1/miR-455-5p and miR-455-5p/CXCL12. Nude mouse xenograft model was used to evaluate the effects of shcircPVT1 and miR-455-5p mimics on tumor growth and metastasis in vivo. Results miR-455-5p was reduced in MTC tissues and cells while circPVT1 was elevated. Their levels were correlated with prognosis of MTC. Overexpression of miR-455-5p or sh-circPVT1 suppressed EMT and MTC cell proliferation, migration and invasion. miR-455-5p targeted CXCL12 while circPVT1 sponged miR-455-5p. Knockdown of CXCL12 or CXCL12/CXCR4 signaling inhibitor reversed the effects of circPVT1 overexpression or miR-455-5p inhibitor on EMT and MTC cell proliferation, migration and invasion. Knockdown of circPVT1 or miR-455-5p overexpression repressed MTC tumor growth and lung metastasis in vivo. Conclusions miR-455-5p suppresses MTC growth and metastasis by targeting CXCL12/CXCR4 signaling pathway while circPVT1 promotes MTC by sponging miR-455-5p. Our study sheds light on the mechanisms of MTC growth and metastasis.https://doi.org/10.1186/s13046-021-01964-0Medullary thyroid cancermiR-455-5pcircPVT1CXCL12/CXCR4 signaling pathway |
| spellingShingle | Xun Zheng Shu Rui Xiao-Fei Wang Xiu-He Zou Yan-Ping Gong Zhi-Hui Li circPVT1 regulates medullary thyroid cancer growth and metastasis by targeting miR-455-5p to activate CXCL12/CXCR4 signaling Journal of Experimental & Clinical Cancer Research Medullary thyroid cancer miR-455-5p circPVT1 CXCL12/CXCR4 signaling pathway |
| title | circPVT1 regulates medullary thyroid cancer growth and metastasis by targeting miR-455-5p to activate CXCL12/CXCR4 signaling |
| title_full | circPVT1 regulates medullary thyroid cancer growth and metastasis by targeting miR-455-5p to activate CXCL12/CXCR4 signaling |
| title_fullStr | circPVT1 regulates medullary thyroid cancer growth and metastasis by targeting miR-455-5p to activate CXCL12/CXCR4 signaling |
| title_full_unstemmed | circPVT1 regulates medullary thyroid cancer growth and metastasis by targeting miR-455-5p to activate CXCL12/CXCR4 signaling |
| title_short | circPVT1 regulates medullary thyroid cancer growth and metastasis by targeting miR-455-5p to activate CXCL12/CXCR4 signaling |
| title_sort | circpvt1 regulates medullary thyroid cancer growth and metastasis by targeting mir 455 5p to activate cxcl12 cxcr4 signaling |
| topic | Medullary thyroid cancer miR-455-5p circPVT1 CXCL12/CXCR4 signaling pathway |
| url | https://doi.org/10.1186/s13046-021-01964-0 |
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