The circDUSP1/miR-429/DLC1 regulatory network affects proliferation, migration, and invasion of triple-negative breast cancer cells
Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype lacking effective targeted therapies, with circular RNAs (circRNAs) emerging as key regulators in cancer progression through competitive endogenous RNA (ceRNA) networks. Although circRNAs function as miRNA sponges in TNBC, the sp...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-11621-7 |
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| author | Canhui Jian Xiaoxue Tian Shuai Luo Jiafei Zeng Jin Li Ting Xu Jinjing Wang |
| author_facet | Canhui Jian Xiaoxue Tian Shuai Luo Jiafei Zeng Jin Li Ting Xu Jinjing Wang |
| author_sort | Canhui Jian |
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| description | Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype lacking effective targeted therapies, with circular RNAs (circRNAs) emerging as key regulators in cancer progression through competitive endogenous RNA (ceRNA) networks. Although circRNAs function as miRNA sponges in TNBC, the specific role of circDUSP1 in the miR-429/DLC1 pathway remains unknown. In this study, a circular RNA, circDUSP1, was identified as differentially expressed in TNBC using an online database. Using TNBC patient tissues and cell lines (MDA-MB-231/MDA-MB-468), we quantified circDUSP1 expression via qRT-PCR. The molecular characteristics of circDUSP1 were identified through methods such as nuclear-cytoplasmic separation, RNase R digestion, and FISH. Assessed the impact of circDUSP1 on TNBC cell proliferation/migration/invasion through functional assays (CCK-8, colony formation, Transwell, etc.). The circDUSP1/miR-429/DLC1 regulatory network’s role in TNBC was validated using dual-luciferase reporter gene, RNA pull-down, and rescue assays. circDUSP1 was significantly downregulated in TNBC tissues and cell lines. circDUSP1 overexpression suppressed TNBC cell proliferation, migration, invasion, and tumor growth in vivo circDUSP1 directly bound miR-429 to relieve its repression of tumor suppressor DLC1 miR-429 mimics attenuated circDUSP1-mediated tumor suppression. circDUSP1 inhibits TNBC progression by acting as a molecular sponge for miR-429 to upregulate DLC1. This regulatory network represents a novel therapeutic target for TNBC. |
| format | Article |
| id | doaj-art-82393df0444f43a6a88091b7b2acfa2d |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-82393df0444f43a6a88091b7b2acfa2d2025-08-20T04:02:56ZengNature PortfolioScientific Reports2045-23222025-07-0115111710.1038/s41598-025-11621-7The circDUSP1/miR-429/DLC1 regulatory network affects proliferation, migration, and invasion of triple-negative breast cancer cellsCanhui Jian0Xiaoxue Tian1Shuai Luo2Jiafei Zeng3Jin Li4Ting Xu5Jinjing Wang6Department of Pathology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Pathology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Pathology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Pathology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Pathology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Pathology, School of Preclinical Medicine, Zunyi Medical UniversityDepartment of Pathology, Affiliated Hospital of Zunyi Medical UniversityAbstract Triple-negative breast cancer (TNBC) is an aggressive subtype lacking effective targeted therapies, with circular RNAs (circRNAs) emerging as key regulators in cancer progression through competitive endogenous RNA (ceRNA) networks. Although circRNAs function as miRNA sponges in TNBC, the specific role of circDUSP1 in the miR-429/DLC1 pathway remains unknown. In this study, a circular RNA, circDUSP1, was identified as differentially expressed in TNBC using an online database. Using TNBC patient tissues and cell lines (MDA-MB-231/MDA-MB-468), we quantified circDUSP1 expression via qRT-PCR. The molecular characteristics of circDUSP1 were identified through methods such as nuclear-cytoplasmic separation, RNase R digestion, and FISH. Assessed the impact of circDUSP1 on TNBC cell proliferation/migration/invasion through functional assays (CCK-8, colony formation, Transwell, etc.). The circDUSP1/miR-429/DLC1 regulatory network’s role in TNBC was validated using dual-luciferase reporter gene, RNA pull-down, and rescue assays. circDUSP1 was significantly downregulated in TNBC tissues and cell lines. circDUSP1 overexpression suppressed TNBC cell proliferation, migration, invasion, and tumor growth in vivo circDUSP1 directly bound miR-429 to relieve its repression of tumor suppressor DLC1 miR-429 mimics attenuated circDUSP1-mediated tumor suppression. circDUSP1 inhibits TNBC progression by acting as a molecular sponge for miR-429 to upregulate DLC1. This regulatory network represents a novel therapeutic target for TNBC.https://doi.org/10.1038/s41598-025-11621-7TNBCTriple-negative breast cancercircDUSP1miR‐429DLC1 |
| spellingShingle | Canhui Jian Xiaoxue Tian Shuai Luo Jiafei Zeng Jin Li Ting Xu Jinjing Wang The circDUSP1/miR-429/DLC1 regulatory network affects proliferation, migration, and invasion of triple-negative breast cancer cells Scientific Reports TNBC Triple-negative breast cancer circDUSP1 miR‐429 DLC1 |
| title | The circDUSP1/miR-429/DLC1 regulatory network affects proliferation, migration, and invasion of triple-negative breast cancer cells |
| title_full | The circDUSP1/miR-429/DLC1 regulatory network affects proliferation, migration, and invasion of triple-negative breast cancer cells |
| title_fullStr | The circDUSP1/miR-429/DLC1 regulatory network affects proliferation, migration, and invasion of triple-negative breast cancer cells |
| title_full_unstemmed | The circDUSP1/miR-429/DLC1 regulatory network affects proliferation, migration, and invasion of triple-negative breast cancer cells |
| title_short | The circDUSP1/miR-429/DLC1 regulatory network affects proliferation, migration, and invasion of triple-negative breast cancer cells |
| title_sort | circdusp1 mir 429 dlc1 regulatory network affects proliferation migration and invasion of triple negative breast cancer cells |
| topic | TNBC Triple-negative breast cancer circDUSP1 miR‐429 DLC1 |
| url | https://doi.org/10.1038/s41598-025-11621-7 |
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