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CircDOCK1 Regulates miR-186/DNMT3A to Promote Osteosarcoma Progression
Zhihui Jin1, Jia Ye1, Sen Chen1
1Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Background:
Circular RNAs (circRNAs), as a class of endogenous RNAs, are implicated in osteosarcoma (OS) progression. However, the functional properties of circDOCK1 in OS have been largely unexplored. The present study demonstrated the regulatory mechanism of circDOCK1 in OS.
Methods:
QRT-PCR and Western blots were used to determine the abundances of circDOCK1, miR-186, and DNMT3A. Cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), colony formation, Transwell, and wound healing assays were used to examine cellular multiplication, motility, and invasion. Luciferase reporter analysis, RNA immunoprecipitation (RIP), and pull-down assays were used to verify target relationships. Xenograft models were used to analyze in vivo function.
Results:
OS tissues and cells showed high levels of circDOCK1. By knocking down circDOCK1, cellular multiplication, motility, and invasion were suppressed. Furthermore, silencing circDOCK1 suppressed the growth of tumor xenografts. According to mechanistic studies, miR-186 targets DNA methyltransferases 3A (DNMT3A) directly and acts as a circDOCK1 target. Furthermore, circDOCK1 upregulated DNMT3A expression through sponging miR-186 to regulate the progression of OS.
Conclusions:
CircDOCK1 promotes OS progression by interacting with miR-186/DNMT3ADNMT3A, representing a novel therapeutic approach.
Insights
Circular RNAs (circRNAs) like circDOCK1 promote osteosarcoma (OS) progression by upregulating DNMT3A via sponging miR-186. Silencing circDOCK1 suppressed tumor growth, offering a potential therapeutic strategy for OS.
Area of Science:
- Molecular Biology
- Oncology
- RNA Biology
Background:
- Circular RNAs (circRNAs) are endogenous RNAs involved in osteosarcoma (OS) progression.
- The specific role of circDOCK1 in OS remains largely uncharacterized.
- This study investigates the regulatory mechanism of circDOCK1 in OS.
Purpose of the Study:
- To elucidate the functional role of circDOCK1 in osteosarcoma.
- To determine the mechanism by which circDOCK1 influences OS progression.
- To identify circDOCK1 as a potential therapeutic target in OS.
Main Methods:
- Quantitative real-time PCR (QRT-PCR) and Western blotting assessed molecule expression.
- Cell proliferation, invasion, and migration were evaluated using CCK-8, EdU, colony formation, Transwell, and wound healing assays.
- Luciferase reporter assays, RNA immunoprecipitation (RIP), and pull-down assays confirmed molecular interactions; in vivo function was assessed using xenograft models.
Main Results:
- circDOCK1 expression was significantly elevated in OS tissues and cells.
- Knockdown of circDOCK1 inhibited OS cell proliferation, motility, and invasion, and suppressed tumor xenograft growth.
- Mechanistic studies revealed that circDOCK1 sponges miR-186, leading to upregulation of its target, DNA methyltransferases 3A (DNMT3A), thereby promoting OS progression.
Conclusions:
- circDOCK1 promotes osteosarcoma progression through the miR-186/DNMT3A axis.
- circDOCK1 represents a novel therapeutic target for osteosarcoma treatment.
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