Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, China.
Pathology Tissue Bank, Qilu Hospital of Shandong University, Jinan, China.
Cell Death Dis. 2022 Sep 8;13(9):776. doi: 10.1038/s41419-022-05216-7.
Numerous studies have shown that circRNAs are aberrantly expressed in various cancers and play a significant role in tumor progression. However, the molecular mechanisms of circRNAs in triple-negative breast cancer (TNBC) remain ambiguous. By intersecting throughput data and qRT-PCR results from tissues and cell lines, circ-TRIO was identified as a potential oncogenic regulator of TNBC. Moreover, circ-TRIO expression was detected in TNBC tissues and was correlated with the recurrence and prognosis of TNBC patients. The circular characteristics of circ-TRIO were verified by RNase R and CHX assays. Functionally, the knockdown of circ-TRIO inhibited the proliferation, migration and invasion of TNBC cells, while the overexpression of circ-TRIO resulted in the opposite impacts. Mechanistically, a dual luciferase reporter assay and RNA immunoprecipitation were performed and indicated that circ-TRIO could combine with miR-432-5p to regulate the expression of coiled-coil domain containing 58 (CCDC58). In summary, our study illustrates that circ-TRIO plays an important role in the progression of TNBC by regulating the miR-432-5p/CCDC58 axis, which could broaden our insight into the underlying mechanisms and provide a novel prognostic marker of TNBC in the clinic.
大量研究表明,circRNAs 在各种癌症中表达异常,在肿瘤进展中发挥重要作用。然而,circRNAs 在三阴性乳腺癌 (TNBC) 中的分子机制仍不清楚。通过将高通量数据与组织和细胞系的 qRT-PCR 结果相交,鉴定出 circ-TRIO 是 TNBC 的潜在致癌调节剂。此外,在 TNBC 组织中检测到 circ-TRIO 的表达,并与 TNBC 患者的复发和预后相关。通过 RNase R 和 CHX 测定验证了 circ-TRIO 的环状特征。功能上,circ-TRIO 的敲低抑制了 TNBC 细胞的增殖、迁移和侵袭,而过表达 circ-TRIO 则产生相反的影响。机制上,进行了双荧光素酶报告基因测定和 RNA 免疫沉淀实验,表明 circ-TRIO 可以与 miR-432-5p 结合,调节卷曲螺旋结构域包含 58 号蛋白 (CCDC58) 的表达。总之,我们的研究表明,circ-TRIO 通过调节 miR-432-5p/CCDC58 轴在 TNBC 的进展中发挥重要作用,这可能拓宽我们对潜在机制的理解,并为临床提供 TNBC 的新型预后标志物。