Down-regulation of circ_0058058 suppresses proliferation, angiogenesis and metastasis in multiple myeloma through miR-338-3p/ATG14 pathway
Abstract Background Multiple myeloma (MM) is one of the most frequently diagnosed hematological malignancy. Dysregulation of circular RNAs (circRNAs) has important impacts on MM process. Herein, this work aimed to investigate the role and mechanism of circ_0058058 in MM progression. Methods Levels o...
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| Format: | Article |
| Language: | English |
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BMC
2021-12-01
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| Series: | Journal of Orthopaedic Surgery and Research |
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| Online Access: | https://doi.org/10.1186/s13018-021-02867-8 |
| _version_ | 1828365014567747584 |
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| author | Lianguo Xue Tao Jia Yuanxin Zhu Lidong Zhao Jianping Mao |
| author_facet | Lianguo Xue Tao Jia Yuanxin Zhu Lidong Zhao Jianping Mao |
| author_sort | Lianguo Xue |
| collection | DOAJ |
| description | Abstract Background Multiple myeloma (MM) is one of the most frequently diagnosed hematological malignancy. Dysregulation of circular RNAs (circRNAs) has important impacts on MM process. Herein, this work aimed to investigate the role and mechanism of circ_0058058 in MM progression. Methods Levels of genes and proteins were detected by real-time reverse transcription PCR (RT-qPCR) and Western blot. CCK-8 assay, colony formation assay, EdU assay, flow cytometry, tube formation assay, transwell assay and Western blot were utilized to detect the proliferation, apoptosis, angiogenesis and metastasis of MM cells. The target relationship between miR-338-3p and circ_0058058 or ATG14 (autophagy related 14) was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. In vivo experiments were performed using Xenograft assay. Results Circ_0058058 was up-regulated in MM bone marrow aspirates and cells, knockdown of circ_0058058 reduced MM cell proliferation, angiogenesis and metastasis, but induced apoptosis in vitro. In a MM xenograft mouse model, circ_0058058 silencing reduced MM tumor growth and cell proliferation. Mechanistically, circ_0058058 acted as a sponge for miR-338-3p to up-regulate ATG14 expression, which was validated to be a target of miR-338-3p. Rescue assay showed that miR-338-3p inhibition reversed the antitumor effects of circ_0058058 knockdown on MM cell. Moreover, forced expression of miR-338-3p suppressed MM cell malignant phenotype, which was abolished by ATG14 up-regulation. Conclusion Circ_0058058 functions as a sponge for miR-338-3p to elevate ATG14 expression to promote MM cell proliferation, metastasis and angiogenesis, affording a potential therapeutic target for MM prevention. |
| first_indexed | 2024-04-14T05:25:02Z |
| format | Article |
| id | doaj.art-1c2cc328ef924ba8b4579c74ba02d3fa |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-04-14T05:25:02Z |
| publishDate | 2021-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-1c2cc328ef924ba8b4579c74ba02d3fa2022-12-22T02:10:01ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2021-12-0116111310.1186/s13018-021-02867-8Down-regulation of circ_0058058 suppresses proliferation, angiogenesis and metastasis in multiple myeloma through miR-338-3p/ATG14 pathwayLianguo Xue0Tao Jia1Yuanxin Zhu2Lidong Zhao3Jianping Mao4Department of Hematology, The First People’s Hospital of LianyungangDepartment of Hematology, The First People’s Hospital of LianyungangDepartment of Hematology, The First People’s Hospital of LianyungangDepartment of Hematology, The First People’s Hospital of LianyungangDepartment of Hematology, The First People’s Hospital of LianyungangAbstract Background Multiple myeloma (MM) is one of the most frequently diagnosed hematological malignancy. Dysregulation of circular RNAs (circRNAs) has important impacts on MM process. Herein, this work aimed to investigate the role and mechanism of circ_0058058 in MM progression. Methods Levels of genes and proteins were detected by real-time reverse transcription PCR (RT-qPCR) and Western blot. CCK-8 assay, colony formation assay, EdU assay, flow cytometry, tube formation assay, transwell assay and Western blot were utilized to detect the proliferation, apoptosis, angiogenesis and metastasis of MM cells. The target relationship between miR-338-3p and circ_0058058 or ATG14 (autophagy related 14) was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. In vivo experiments were performed using Xenograft assay. Results Circ_0058058 was up-regulated in MM bone marrow aspirates and cells, knockdown of circ_0058058 reduced MM cell proliferation, angiogenesis and metastasis, but induced apoptosis in vitro. In a MM xenograft mouse model, circ_0058058 silencing reduced MM tumor growth and cell proliferation. Mechanistically, circ_0058058 acted as a sponge for miR-338-3p to up-regulate ATG14 expression, which was validated to be a target of miR-338-3p. Rescue assay showed that miR-338-3p inhibition reversed the antitumor effects of circ_0058058 knockdown on MM cell. Moreover, forced expression of miR-338-3p suppressed MM cell malignant phenotype, which was abolished by ATG14 up-regulation. Conclusion Circ_0058058 functions as a sponge for miR-338-3p to elevate ATG14 expression to promote MM cell proliferation, metastasis and angiogenesis, affording a potential therapeutic target for MM prevention.https://doi.org/10.1186/s13018-021-02867-8circ_0058058miR-338-3pATG14ApoptosisMetastasisMultiple myeloma |
| spellingShingle | Lianguo Xue Tao Jia Yuanxin Zhu Lidong Zhao Jianping Mao Down-regulation of circ_0058058 suppresses proliferation, angiogenesis and metastasis in multiple myeloma through miR-338-3p/ATG14 pathway Journal of Orthopaedic Surgery and Research circ_0058058 miR-338-3p ATG14 Apoptosis Metastasis Multiple myeloma |
| title | Down-regulation of circ_0058058 suppresses proliferation, angiogenesis and metastasis in multiple myeloma through miR-338-3p/ATG14 pathway |
| title_full | Down-regulation of circ_0058058 suppresses proliferation, angiogenesis and metastasis in multiple myeloma through miR-338-3p/ATG14 pathway |
| title_fullStr | Down-regulation of circ_0058058 suppresses proliferation, angiogenesis and metastasis in multiple myeloma through miR-338-3p/ATG14 pathway |
| title_full_unstemmed | Down-regulation of circ_0058058 suppresses proliferation, angiogenesis and metastasis in multiple myeloma through miR-338-3p/ATG14 pathway |
| title_short | Down-regulation of circ_0058058 suppresses proliferation, angiogenesis and metastasis in multiple myeloma through miR-338-3p/ATG14 pathway |
| title_sort | down regulation of circ 0058058 suppresses proliferation angiogenesis and metastasis in multiple myeloma through mir 338 3p atg14 pathway |
| topic | circ_0058058 miR-338-3p ATG14 Apoptosis Metastasis Multiple myeloma |
| url | https://doi.org/10.1186/s13018-021-02867-8 |
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