CircECE1 promotes osteosarcoma progression through regulating RAB3D by sponging miR-588

Abstract Background Circular RNAs (circRNAs) have been confirmed to be involved in cancer pathogenesis. However, the underlying mechanism of circRNA endothelin converting enzyme 1 (circECE1) in osteosarcoma (OS) development is still not understood. Methods The expression levels of circECE1, microRNA...

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Main Authors: Zhizhong Liang, Yuxia Shi, Zhe Guan
Format: Article
Language:English
Published: BMC 2023-08-01
Series:Journal of Orthopaedic Surgery and Research
Subjects:
Online Access:https://doi.org/10.1186/s13018-023-04045-4
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author Zhizhong Liang
Yuxia Shi
Zhe Guan
author_facet Zhizhong Liang
Yuxia Shi
Zhe Guan
author_sort Zhizhong Liang
collection DOAJ
description Abstract Background Circular RNAs (circRNAs) have been confirmed to be involved in cancer pathogenesis. However, the underlying mechanism of circRNA endothelin converting enzyme 1 (circECE1) in osteosarcoma (OS) development is still not understood. Methods The expression levels of circECE1, microRNA-588 (miR-588) and RAB3D, member RAS oncogene family (RAB3D) were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. OS cell proliferation was assessed by cell counting kit-8 (CCK-8) assay and 5-ethynyl-2’-deoxyuridine (EdU) assay. OS cell apoptosis rate and metastasis were identified by flow cytometry and transwell assay. Dual-luciferase reporter analysis and RNA immunoprecipitation (RIP) assay were performed to confirm the interactions among circECE1, miR-588 and RAB3D. Xenograft tumor models were established to explore circECE1 function in vivo. Immunohistochemistry (IHC) assay was applied to analyze RAB3D level after circECE1 knockdown. Results In OS, circECE1 expression was higher than that in normal chondroma tissues. High levels of circECE1 were positively linked to OS cell viability, proliferation, migration and invasion, and negatively linked to OS cell apoptosis rate. It was found that circECE1 was a miR-588 sponge, and miR-588 inhibitor abrogated the influence of si-circECE1 on OS cells. MiR-588 targeted RAB3D to further regulate the pathological process of OS. Moreover, silencing circECE1 blocked OS tumor growth in vivo. Conclusion We elucidated the function of a novel circECE1/miR-588/RAB3D axis in OS progression.
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spelling doaj.art-281cbdbe61c9462a82068ec02339f7382023-11-20T10:20:57ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2023-08-0118111310.1186/s13018-023-04045-4CircECE1 promotes osteosarcoma progression through regulating RAB3D by sponging miR-588Zhizhong Liang0Yuxia Shi1Zhe Guan2Department of Bone and Soft Tissue Oncology, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical UniversityDepartment of Bone and Soft Tissue Oncology, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical UniversityDepartment of Bone and Soft Tissue Oncology, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical UniversityAbstract Background Circular RNAs (circRNAs) have been confirmed to be involved in cancer pathogenesis. However, the underlying mechanism of circRNA endothelin converting enzyme 1 (circECE1) in osteosarcoma (OS) development is still not understood. Methods The expression levels of circECE1, microRNA-588 (miR-588) and RAB3D, member RAS oncogene family (RAB3D) were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. OS cell proliferation was assessed by cell counting kit-8 (CCK-8) assay and 5-ethynyl-2’-deoxyuridine (EdU) assay. OS cell apoptosis rate and metastasis were identified by flow cytometry and transwell assay. Dual-luciferase reporter analysis and RNA immunoprecipitation (RIP) assay were performed to confirm the interactions among circECE1, miR-588 and RAB3D. Xenograft tumor models were established to explore circECE1 function in vivo. Immunohistochemistry (IHC) assay was applied to analyze RAB3D level after circECE1 knockdown. Results In OS, circECE1 expression was higher than that in normal chondroma tissues. High levels of circECE1 were positively linked to OS cell viability, proliferation, migration and invasion, and negatively linked to OS cell apoptosis rate. It was found that circECE1 was a miR-588 sponge, and miR-588 inhibitor abrogated the influence of si-circECE1 on OS cells. MiR-588 targeted RAB3D to further regulate the pathological process of OS. Moreover, silencing circECE1 blocked OS tumor growth in vivo. Conclusion We elucidated the function of a novel circECE1/miR-588/RAB3D axis in OS progression.https://doi.org/10.1186/s13018-023-04045-4circECE1Microrna-588RAB3DMember RAS oncogene familyOsteosarcoma
spellingShingle Zhizhong Liang
Yuxia Shi
Zhe Guan
CircECE1 promotes osteosarcoma progression through regulating RAB3D by sponging miR-588
Journal of Orthopaedic Surgery and Research
circECE1
Microrna-588
RAB3D
Member RAS oncogene family
Osteosarcoma
title CircECE1 promotes osteosarcoma progression through regulating RAB3D by sponging miR-588
title_full CircECE1 promotes osteosarcoma progression through regulating RAB3D by sponging miR-588
title_fullStr CircECE1 promotes osteosarcoma progression through regulating RAB3D by sponging miR-588
title_full_unstemmed CircECE1 promotes osteosarcoma progression through regulating RAB3D by sponging miR-588
title_short CircECE1 promotes osteosarcoma progression through regulating RAB3D by sponging miR-588
title_sort circece1 promotes osteosarcoma progression through regulating rab3d by sponging mir 588
topic circECE1
Microrna-588
RAB3D
Member RAS oncogene family
Osteosarcoma
url https://doi.org/10.1186/s13018-023-04045-4
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AT yuxiashi circece1promotesosteosarcomaprogressionthroughregulatingrab3dbyspongingmir588
AT zheguan circece1promotesosteosarcomaprogressionthroughregulatingrab3dbyspongingmir588