miR-653-5p suppresses the viability and migration of fibroblast-like synoviocytes by targeting FGF2 and inactivation of the Wnt/beta-catenin pathway
Abstract Background Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Several studies reported that fibroblast-like synoviocytes (FLSs) and miRNAs are associated with RA pathogenesis. This study explored the function of miR-653-5p in the regulation of human fibroblast-like synovioc...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13018-021-02887-4 |
| _version_ | 1817997808005808128 |
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| author | Peilong Dong Xiaobo Tang Jian Wang Botao Zhu Zhiyun Li |
| author_facet | Peilong Dong Xiaobo Tang Jian Wang Botao Zhu Zhiyun Li |
| author_sort | Peilong Dong |
| collection | DOAJ |
| description | Abstract Background Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Several studies reported that fibroblast-like synoviocytes (FLSs) and miRNAs are associated with RA pathogenesis. This study explored the function of miR-653-5p in the regulation of human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) cells. Methods The mRNA and protein levels of genes were measured by RT-qPCR and western blot, respectively. MTT, wound healing, and invasion assays were used to evaluate the viability and metastasis of FLSs. Luciferase reporter and RNA pull-down assays were employed to determine the interaction between miR-653-5p and FGF2. Results RT-qPCR results demonstrated that miR-653-5p expression was decreased and FGF2 level was increased in synovial tissues and FLSs of RA. Moreover, the viability and metastasis of FLSs were accelerated by miR-653-5p addition, which was restrained by miR-653-5p suppression. Furthermore, we demonstrated that levels of Rac1, Cdc42, and RhoA were decreased after miR-653-5p addition. Besides, luciferase reporter and RNA pull-down assays implied that miR-653-5p targeted the 3′-UTR of FGF2. Functional assays showed that FGF2 overexpression neutralized the suppressive effects of miR-653-5p addition on HFLS-RA cell viability, metastasis, and the levels of Rho family proteins. Meanwhile, the levels of β-catenin, cyclin D1, and c-myc were declined by miR-653-5p supplementation, but enhanced by FGF2 addition. Conclusion In sum, we manifested that miR-653-5p restrained HFLS-RA cell viability and metastasis via targeting FGF2 and repressing the Wnt/beta-Catenin pathway. |
| first_indexed | 2024-04-14T02:43:45Z |
| format | Article |
| id | doaj.art-ac8f39d0f6474990bf45a79511214b69 |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-04-14T02:43:45Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-ac8f39d0f6474990bf45a79511214b692022-12-22T02:16:42ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2022-01-011711810.1186/s13018-021-02887-4miR-653-5p suppresses the viability and migration of fibroblast-like synoviocytes by targeting FGF2 and inactivation of the Wnt/beta-catenin pathwayPeilong Dong0Xiaobo Tang1Jian Wang2Botao Zhu3Zhiyun Li4Department of Orthopedics, Affiliated Jianhu Hospital of Nantong UniversityDepartment of Orthopedics, Affiliated Jianhu Hospital of Nantong UniversityDepartment of Orthopedics, Affiliated Jianhu Hospital of Nantong UniversityDepartment of Orthopedics, Affiliated Jianhu Hospital of Nantong UniversityDepartment of Orthopedics, Affiliated Jianhu Hospital of Nantong UniversityAbstract Background Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Several studies reported that fibroblast-like synoviocytes (FLSs) and miRNAs are associated with RA pathogenesis. This study explored the function of miR-653-5p in the regulation of human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) cells. Methods The mRNA and protein levels of genes were measured by RT-qPCR and western blot, respectively. MTT, wound healing, and invasion assays were used to evaluate the viability and metastasis of FLSs. Luciferase reporter and RNA pull-down assays were employed to determine the interaction between miR-653-5p and FGF2. Results RT-qPCR results demonstrated that miR-653-5p expression was decreased and FGF2 level was increased in synovial tissues and FLSs of RA. Moreover, the viability and metastasis of FLSs were accelerated by miR-653-5p addition, which was restrained by miR-653-5p suppression. Furthermore, we demonstrated that levels of Rac1, Cdc42, and RhoA were decreased after miR-653-5p addition. Besides, luciferase reporter and RNA pull-down assays implied that miR-653-5p targeted the 3′-UTR of FGF2. Functional assays showed that FGF2 overexpression neutralized the suppressive effects of miR-653-5p addition on HFLS-RA cell viability, metastasis, and the levels of Rho family proteins. Meanwhile, the levels of β-catenin, cyclin D1, and c-myc were declined by miR-653-5p supplementation, but enhanced by FGF2 addition. Conclusion In sum, we manifested that miR-653-5p restrained HFLS-RA cell viability and metastasis via targeting FGF2 and repressing the Wnt/beta-Catenin pathway.https://doi.org/10.1186/s13018-021-02887-4miR-653-5pFGF2Rheumatoid arthritisFibroblast-like synoviocytes |
| spellingShingle | Peilong Dong Xiaobo Tang Jian Wang Botao Zhu Zhiyun Li miR-653-5p suppresses the viability and migration of fibroblast-like synoviocytes by targeting FGF2 and inactivation of the Wnt/beta-catenin pathway Journal of Orthopaedic Surgery and Research miR-653-5p FGF2 Rheumatoid arthritis Fibroblast-like synoviocytes |
| title | miR-653-5p suppresses the viability and migration of fibroblast-like synoviocytes by targeting FGF2 and inactivation of the Wnt/beta-catenin pathway |
| title_full | miR-653-5p suppresses the viability and migration of fibroblast-like synoviocytes by targeting FGF2 and inactivation of the Wnt/beta-catenin pathway |
| title_fullStr | miR-653-5p suppresses the viability and migration of fibroblast-like synoviocytes by targeting FGF2 and inactivation of the Wnt/beta-catenin pathway |
| title_full_unstemmed | miR-653-5p suppresses the viability and migration of fibroblast-like synoviocytes by targeting FGF2 and inactivation of the Wnt/beta-catenin pathway |
| title_short | miR-653-5p suppresses the viability and migration of fibroblast-like synoviocytes by targeting FGF2 and inactivation of the Wnt/beta-catenin pathway |
| title_sort | mir 653 5p suppresses the viability and migration of fibroblast like synoviocytes by targeting fgf2 and inactivation of the wnt beta catenin pathway |
| topic | miR-653-5p FGF2 Rheumatoid arthritis Fibroblast-like synoviocytes |
| url | https://doi.org/10.1186/s13018-021-02887-4 |
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