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Published on: March 30, 2019
Circ_0001777 Affects Triple-negative Breast Cancer Progression Through the miR-95-3p/AKAP12 Axis
Zhuorong Chen1, Xumeng Gong1, Chun Cheng2
1Department of Head and neck &Breast Surgery, Yue Bei People's Hospital, Shaoguan City, Guangdong Province, China.
Background:
Triple Negative Breast Cancer (TNBC) is 1 of the most serious cancer. Circular RNA_0001777 (circ_0001777) expression was decreased in TNBC tissues. However, the molecular mechanism of circ_0001777 remains unknown.
Methods:
The expression of circ_0001777, microRNA-95-3p (miR-95-3p) and A-kinase anchor protein 12 (AKAP12) were detected by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR). A series of in vitro experiments were designed to explore the function of circ_0001777 in TNBC cells and the regulatory mechanism between circ_0001777 and miR-95-3p and AKAP12 in TNBC cells. Western blot examined the relative protein levels in TNBC cells. Bioinformatics prediction site predicted the relationship between miR-95-3p and circ_0001777 or AKAP12 and was verified by Dual-luciferase reporter assays. The xenotransplantation model was established to study the role of circ_0001777 in vivo.
Results:
The expression of circ_0001777 and AKAP12 was decreased in TNBC tissues, while the expression of miR-95-3p was increased. Circ_0001777 can sponge miR-95-3p, and AKAP12 is the target of miR-95-3p. In vitro complement experiments, overexpression of circ_0001777 significantly decreased the malignant behavior of TNBC, while co-transfection of miR-95-3p partially up-regulated this change. In addition, AKAP12 knockdown increased the proliferation, migration, and invasion of TNBC cells inhibited by overexpression of circ_0001777. Mechanically, circ_0001777 regulates AKAP12 expression in TNBC cells by sponge miR-95-3p. In addition, in vivo studies have shown that overexpression of circ_0001777 inhibits tumor growth.
Conclusion:
Overexpression of circ_0001777 decreased proliferation, migration, and invasion of TNBC cells by regulating the miR-95-3p/AKAP12 axis, suggesting that circ_0001777/miR-95-3p/AKAP12 axis may be a potential regulatory mechanism for the treatment of TNBC.
Insights
Circular RNA_0001777 (circ_0001777) suppresses Triple Negative Breast Cancer (TNBC) by regulating the miR-95-3p/AKAP12 pathway. This finding suggests circ_0001777 as a potential therapeutic target for TNBC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Triple Negative Breast Cancer (TNBC) is an aggressive malignancy with limited therapeutic options.
- Circular RNA_0001777 (circ_0001777) expression is significantly reduced in TNBC tissues, indicating its potential role as a tumor suppressor.
Purpose of the Study:
- To elucidate the molecular mechanism of circ_0001777 in TNBC.
- To investigate the regulatory relationship between circ_0001777, microRNA-95-3p (miR-95-3p), and A-kinase anchor protein 12 (AKAP12) in TNBC cells.
Main Methods:
- Quantitative real-time fluorescence polymerase chain reaction (qRT-PCR) and Western blot were used to assess gene and protein expression.
- In vitro cell experiments and in vivo xenotransplantation models were employed to evaluate the functional role of circ_0001777.
- Bioinformatics and Dual-luciferase reporter assays confirmed the interactions between circ_0001777, miR-95-3p, and AKAP12.
Main Results:
- Circ_0001777 and AKAP12 expression were downregulated, while miR-95-3p was upregulated in TNBC tissues.
- Circ_0001777 acted as a sponge for miR-95-3p, and AKAP12 was identified as a direct target of miR-95-3p.
- Overexpression of circ_0001777 inhibited TNBC cell proliferation, migration, and invasion, an effect partially reversed by miR-95-3p co-transfection and exacerbated by AKAP12 knockdown.
Conclusions:
- The circ_0001777/miR-95-3p/AKAP12 axis plays a crucial role in regulating TNBC progression.
- Circ_0001777 functions as a tumor suppressor in TNBC by inhibiting proliferation, migration, and invasion through the miR-95-3p/AKAP12 pathway.
- Targeting the circ_0001777/miR-95-3p/AKAP12 axis presents a promising therapeutic strategy for TNBC.
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