Wei Dexian, Zhang Fan, Li Min, Fan Zhimin, Ma Jiulong, Ji Jiahua, Qiao Sennan, Huang Peng, Zhang Wenqing, Fan Kaiqi, Li Lu, Zheng Wentao, Li Xiangjun, Ren Liqun
Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China.
Qingdao Municipal Hospital Qingdao, Shandong 266000, China.
Biochem Pharmacol. 2025 Feb;232:116719. doi: 10.1016/j.bcp.2024.116719. Epub 2024 Dec 20.
Triple-negative breast cancer (TNBC) is an aggressive molecular subtype of breast cancer characterized by a high recurrence rate, poor prognosis, and elevated mortality. Identifying novel molecular targets is crucial for developing more effective therapeutic strategies against TNBC. Recent studies have highlighted the role of circular RNAs (circRNAs) in the progression of TNBC. In this study, we identified and validated that circDUSP16 (hsa_circ_0003855) is significantly upregulated in TNBC cells, tissues, and plasma exosomes. Functional assays in vitro demonstrated that overexpression of circDUSP16 promoted the proliferation, migration and invasion of TNBC cells, weathers circDUSP16 knockdown exerted the opposite effect. In vivo studies confirmed that circDUSP16 knockdown can inhibit tumor growth. Using bioinformatics analysis, circDUSP16/miR-1224-3p/TFDP2 pathway was predicted and cascaded. Mechanistically, circDUSP16 was shown to promote the progression of TNBC via the miR-1224-3p/TFDP2 axis. Additionally, THP, a commonly used anthracycline chemotherapy drug, was found to downregulate circDUSP16, suggesting that its therapeutic effects on TNBC may be mediated through circDUSP16/miR-1224-3p/TFDP2 pathway. Our findings suggest that circDUSP16 is a promising biomarker and potential therapeutic target for TNBC.
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌分子亚型，其特征为高复发率、预后差和死亡率升高。识别新的分子靶点对于开发更有效的TNBC治疗策略至关重要。最近的研究强调了环状RNA（circRNA）在TNBC进展中的作用。在本研究中，我们鉴定并验证了circDUSP16（hsa_circ_0003855）在TNBC细胞、组织和血浆外泌体中显著上调。体外功能实验表明，circDUSP16的过表达促进了TNBC细胞的增殖、迁移和侵袭，而circDUSP16敲低则产生相反的效果。体内研究证实，circDUSP16敲低可抑制肿瘤生长。通过生物信息学分析，预测并串联了circDUSP16/miR-1224-3p/TFDP2通路。机制上，circDUSP16通过miR-1224-3p/TFDP2轴促进TNBC的进展。此外，发现常用的蒽环类化疗药物THP可下调circDUSP16，表明其对TNBC的治疗作用可能通过circDUSP16/miR-1224-3p/TFDP2通路介导。我们的研究结果表明，circDUSP16是TNBC一个有前景的生物标志物和潜在治疗靶点。
