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Circular RNA circTADA2A promotes osteosarcoma progression and metastasis by sponging miR-203a-3p and regulating CREB3
Yizheng Wu1,2, Ziang Xie1,2, Junxin Chen1,2
1Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China.
Background:
As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. However, little is known about the role of circTADA2A, also named hsa_circ_0043278, in osteosarcoma (OS).
Methods:
CircTADA2A was selected from a previously reported circRNA microarray comparing OS cell lines and normal bone cells. QRT-PCR was used to detect the expression of circTADA2A in OS tissue and cell lines. Luciferase reporter, RNA immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were performed to confirm the binding of circTADA2A with miR-203a-3p. OS cells were stably transfected with lentiviruses, and Transwell migration, Matrigel invasion, colony formation, proliferation, apoptosis, Western blotting, and in vivo tumorigenesis and metastasis assays were employed to evaluate the roles of circTADA2A, miR-203a-3p and CREB3.
Results:
Our findings demonstrated that circTADA2A was highly expressed in both OS tissue and cell lines, and circTADA2A inhibition attenuated the migration, invasion and proliferation of OS cells in vitro as well as tumorigenesis and metastasis in vivo. A mechanistic study revealed that circTADA2A could readily sponge miR-203a-3p to upregulate the expression of CREB3, which was identified as a driver gene in OS. Furthermore, miR-203a-3p inhibition or CREB3 overexpression could reverse the circTADA2A silencing-induced impairment of malignant tumor behavior.
Conclusions:
CircTADA2A functions as a tumor promoter in OS to increase malignant tumor behavior through the miR-203a-3p/CREB3 axis, which could be a novel target for OS therapy.
Insights
Circular RNA TADA2A (circTADA2A) promotes osteosarcoma progression by sponging miR-203a-3p and upregulating CREB3. Inhibiting circTADA2A may offer a novel therapeutic strategy for osteosarcoma.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Circular RNAs (circRNAs) are key regulators of gene expression.
- circRNAs play significant roles in cancer progression.
- The function of circTADA2A in osteosarcoma (OS) remains largely unknown.
Purpose of the Study:
- To investigate the role of circTADA2A in osteosarcoma.
- To elucidate the molecular mechanism of circTADA2A in OS progression.
- To explore circTADA2A as a potential therapeutic target for OS.
Main Methods:
- circRNA microarray analysis and QRT-PCR to detect circTADA2A expression in OS.
- Luciferase reporter, RIP, and RNA pull-down assays to confirm circTADA2A/miR-203a-3p interaction.
- In vitro and in vivo assays to evaluate the functional roles of circTADA2A, miR-203a-3p, and CREB3 in OS.
Main Results:
- circTADA2A is highly expressed in OS tissues and cell lines.
- circTADA2A inhibition suppressed OS cell migration, invasion, proliferation, tumorigenesis, and metastasis.
- circTADA2A sponges miR-203a-3p, upregulating CREB3 expression, a driver gene in OS.
Conclusions:
- circTADA2A acts as a tumor promoter in osteosarcoma.
- The circTADA2A/miR-203a-3p/CREB3 axis drives malignant behaviors in OS.
- circTADA2A represents a potential novel therapeutic target for osteosarcoma.
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