Department of General Surgery, The Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, 215004, Suzhou, Jiangsu Province, China.
Surgery Department, Suzhou Wuzhong People's Hospital, 215128, Suzhou, Jiangsu Province, China.
BMC Cancer. 2024 Mar 1;24(1):278. doi: 10.1186/s12885-024-12007-0.
Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer (BC). The circRNA-miRNA‒mRNA axis is a promising biomarker for the early diagnosis and prognosis of BC. However, the critical circRNA mediators involved in TNBC progression and the underlying regulatory mechanism involved remain largely unclear.
In this study, we carried out a circRNA microarray analysis of 6 TNBC patients and performed a gene ontology (GO) analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to characterize important circRNAs involved in TNBC progression. The interaction between circRNAs and miRNAs was determined by dual luciferase and RNA immunoprecipitation (RIP) assays. Moreover, Transwell, wound healing and Cell Counting Kit-8 (CCK8) assays were performed with altered circRNA or miRNA expression in MDA-MB-231 and BT-549 cells to investigate the roles of these genes in cell invasion, migration and proliferation.
A total of 78 circRNAs were differentially expressed in TNBC tissues, and the hsa_circ_0045881 level was significantly decreased in TNBC tissues and cells. Lentivirus-mediated hsa_circ_0045881 overexpression in MDA-MB-231 and BT-549 cells significantly reduced cell invasion and migration capacity. Additionally, hsa_circ_0045881 interacted with miR-214-3p in MDA-MB-231 cells. miR-214-3p mimics in MDA-MB-231 and BT-549 cells significantly enhanced cell invasion, migration and proliferation, but the other combinations of inhibitors had opposite effects on cell activity.
Our data indicated that the circRNA has_circ_0045881 plays key roles in TNBC progression and that hsa_circ_0045881 might act as a sponge for miR-214-3p to modulate its levels in TNBC cells, thereby regulating cell invasion, metastasis and proliferation. hsa_circ_004588 might be a potential prognostic marker and therapeutic target for TNBC.
三阴性乳腺癌（TNBC）是乳腺癌（BC）中最致命的亚型。circRNA-miRNA-mRNA 轴是 BC 早期诊断和预后的有前途的生物标志物。然而，涉及 TNBC 进展的关键 circRNA 介质及其潜在的调节机制在很大程度上仍不清楚。
在这项研究中，我们对 6 名 TNBC 患者进行了 circRNA 微阵列分析，并进行了基因本体论（GO）分析。京都基因与基因组百科全书（KEGG）分析用于描述与 TNBC 进展相关的重要 circRNA。通过双荧光素酶和 RNA 免疫沉淀（RIP）测定确定 circRNA 和 miRNA 之间的相互作用。此外，通过改变 circRNA 或 miRNA 在 MDA-MB-231 和 BT-549 细胞中的表达，进行 Transwell、伤口愈合和细胞计数试剂盒-8（CCK8）测定，以研究这些基因在细胞侵袭、迁移和增殖中的作用。
在 TNBC 组织中共有 78 个 circRNA 表达差异，hsa_circ_0045881 在 TNBC 组织和细胞中的水平显著降低。慢病毒介导的 hsa_circ_0045881 在 MDA-MB-231 和 BT-549 细胞中的过表达显著降低了细胞侵袭和迁移能力。此外，hsa_circ_0045881 与 MDA-MB-231 细胞中的 miR-214-3p 相互作用。miR-214-3p 模拟物在 MDA-MB-231 和 BT-549 细胞中显著增强了细胞侵袭、迁移和增殖，但抑制剂的其他组合对细胞活性有相反的影响。
我们的数据表明，circRNA hsa_circ_0045881 在 TNBC 进展中起关键作用，hsa_circ_0045881 可能作为 miR-214-3p 的海绵，调节其在 TNBC 细胞中的水平，从而调节细胞侵袭、转移和增殖。hsa_circ_004588 可能是 TNBC 的潜在预后标志物和治疗靶点。
