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Published on: March 30, 2019
The Novel Circular RNA Circ-PGAP3 Promotes the Proliferation and Invasion of Triple Negative Breast Cancer by
Dabao He1, Xiaoling Yang2, Wenbin Kuang1
1Department of Laboratory Medicine, Shenzhen Longhua District Central Hospital, Shenzhen 518110, People's Republic of China.
Background:
Triple negative breast cancer (TNBC), a special subtype of breast cancer, is characterized by high recurrence, mortality and few treatments. To date, the key factors contributing to TNBC progression have not been fully identified. In the current study, we found a TNBC-related circular RNA (circRNA), circ-PGAP3, and explored its biological function, clinical significance and potential mechanism of action.
Materials And Methods:
The functional assay was carried out using CCK-8, colony formation and Transwell invasion assays. RIP, RNA pull-down and luciferase reporter assays were used to test the correlation between circ-PGAP3, miR-330-3p and Myc. The animal model was employed to verify the function of circ-PGAP3 in vivo.
Results:
Circ-PGAP3 expression was significantly increased in TNBC tissues. High circ-PGAP3 was closely associated with large tumor size, lymph node metastasis, later TNM stage and dismal outcome. Through performing a series of in vitro and in vivo experiments, we found that circ-PGAP3 promoted TNBC cell growth and metastasis via sponging and inhibiting miR-330-3p, resulting in the upregulation of proto-oncogene Myc. Importantly, circ-PGAP3 expression was positively correlated with the Myc protein level but negatively correlated with miR-330-3p expression in TNBC tissues. Moreover, silencing of miR-330-3p or overexpression of Myc could effectively rescue the weakened malignant phenotype induced by circ-PGAP3 knockdown.
Conclusion:
Our results unveil the important driving role of circ-PGAP3 in TNBC development and progression, which provides a candidate therapeutic target for TNBC patients.
Insights
Circular RNA circ-PGAP3 promotes triple-negative breast cancer (TNBC) growth and metastasis by inhibiting miR-330-3p and upregulating Myc. This finding offers a potential therapeutic target for TNBC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Triple-negative breast cancer (TNBC) presents significant clinical challenges due to high recurrence rates, mortality, and limited treatment options.
- Key factors driving TNBC progression remain incompletely understood, necessitating further research into novel molecular mechanisms.
- Circular RNAs (circRNAs) are emerging as critical regulators in various cancers, including breast cancer.
Purpose of the Study:
- To identify and characterize a novel circular RNA, circ-PGAP3, involved in triple-negative breast cancer.
- To elucidate the biological functions and clinical significance of circ-PGAP3 in TNBC.
- To investigate the underlying molecular mechanism by which circ-PGAP3 influences TNBC progression.
Main Methods:
- Functional assays including CCK-8, colony formation, and Transwell invasion assays were performed.
- RNA immunoprecipitation (RIP), RNA pull-down, and luciferase reporter assays were utilized to explore interactions between circ-PGAP3, miR-330-3p, and Myc.
- In vivo experiments using an animal model were conducted to validate the role of circ-PGAP3.
Main Results:
- Circ-PGAP3 expression is significantly elevated in TNBC tissues and correlates with advanced tumor stage, metastasis, and poor prognosis.
- Circ-PGAP3 promotes TNBC cell growth and metastasis by acting as a sponge for miR-330-3p, leading to increased proto-oncogene Myc expression.
- Experimental validation confirmed a positive correlation between circ-PGAP3 and Myc levels, and a negative correlation with miR-330-3p in TNBC tissues.
Conclusions:
- Circ-PGAP3 plays a crucial role in driving the development and progression of triple-negative breast cancer.
- The circ-PGAP3/miR-330-3p/Myc axis represents a significant pathway in TNBC pathogenesis.
- Circ-PGAP3 emerges as a promising candidate therapeutic target for improving outcomes in TNBC patients.
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