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Updated: Aug 2, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Silencing circular RNA hsa_circABCC1 inhibits osteosarcoma progression through down-regulating HDAC4 via sponging
Kai Wang1, Na Wang2, Jingsheng Liu1
1Department of Orthopedics, Second Hospital of Lanzhou University, Lanzhou, China.
Background:
Circular RNA (circRNA) has been shown to play an important regulatory role in the development of various cancers, including osteosarcoma (OS). However, the role of circRNA ABCC1 (circABCC1) in OS was still poorly understood. The aim of our study was to investigate the role of circABCC1 in OS progression and its potential molecular mechanisms.
Methods:
The expression of circABCC1, microRNA-591 (miR-591) and histone deacetylase 4 (HDAC4) in OS tissues or cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) analyses. In vitro experiments, the viability, proliferation, apoptosis, migration, invasion and autophagy of U2OS and HOS cells were assessed in vitro using cell counting kit-8 (CCK-8) assay, 5-ethynyl-29-deoxyuridine (EdU) assay, flow cytometry (FCM) assay, transwell migration and invasion assays (transwell) and WB assay, respectively. Interactions between circABCC1 and miR-591, miR-591 and HDAC4 were confirmed using a dual luciferase reporter gene assay system. The oncogenic role of circABCC1 in OS in vivo was examined by establishing a tumor xenograft model.
Results:
CircABCC1 was significantly elevated in OS tissues (about 3.1-folds) and cells (U2OS (about 2.1-folds) and HOS (about 2.8-folds)) compared with the control (p < .05). Silencing of circABCC1 significantly reduced the viability and proliferation, promoted apoptosis, impaired migration and invasion, and increased autophagy of U2OS and HOS cells (p < .05). In addition, miR-591 was confirmed to be a target of circABCC1, exerting an opposite effect to circABCC1 (p < .05). MiR-591 attenuation in U2OS and HOS cells was able to reply to the inhibition of cell proliferation, migration and invasion as well as promotion of cell apoptosis and autophagy mediated by silencing circABCC1 (p < .05). HDAC4 was verified to be the target gene of miR-591 in U2OS and HOS cells and was regulated by the circABCC1/miR-591 axis (p < .05), and restoration of HDAC4 levels in U2OS and HOS cells was able to restore the altered cellular function caused by silencing circABCC1 (p < .05). In addition, knockdown of circABCC1 attenuated tumor growth in vivo (p < .05).
Conclusion:
Silencing of circABCC1 inhibits osteosarcoma progression by attenuating HDAC4 expression through sponging miR-591.
Insights
Circular RNA ABCC1 (circABCC1) promotes osteosarcoma (OS) progression by increasing HDAC4 expression via sponging miR-591. Silencing circABCC1 inhibits OS cell viability, proliferation, migration, and invasion while promoting apoptosis and autophagy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are crucial regulators in cancer development.
- The specific role of circRNA ABCC1 (circABCC1) in osteosarcoma (OS) remains largely uncharacterized.
- Understanding circABCC1's function is vital for developing novel OS therapeutic strategies.
Purpose of the Study:
- To elucidate the role of circABCC1 in the progression of osteosarcoma.
- To investigate the underlying molecular mechanisms of circABCC1 in OS.
- To explore the potential of targeting circABCC1 for OS treatment.
Main Methods:
- Quantitative real-time PCR and Western blot were used to measure circABCC1, miR-591, and HDAC4 expression in OS tissues and cells.
- In vitro assays (CCK-8, EdU, FCM, Transwell) assessed cell viability, proliferation, apoptosis, migration, and invasion.
- Dual luciferase reporter assays confirmed interactions between circABCC1/miR-591 and miR-591/HDAC4.
- A tumor xenograft model evaluated the in vivo oncogenic role of circABCC1.
Main Results:
- CircABCC1 expression was significantly upregulated in OS tissues and cells.
- Silencing circABCC1 inhibited OS cell proliferation, viability, migration, and invasion, while promoting apoptosis and autophagy.
- CircABCC1 acted as a sponge for miR-591, and miR-591 targeted HDAC4, forming the circABCC1/miR-591/HDAC4 axis.
- Knockdown of circABCC1 suppressed tumor growth in vivo.
Conclusions:
- CircABCC1 promotes osteosarcoma progression.
- The circABCC1/miR-591/HDAC4 axis plays a critical role in OS development.
- Silencing circABCC1 inhibits OS progression by downregulating HDAC4 expression via sponging miR-591.
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