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环状 RNA 转录物相互作用蛋白通过调控 miR-432-5p/CCDC58 轴促进三阴性乳腺癌的进展。

Circ-TRIO promotes TNBC progression by regulating the miR-432-5p/CCDC58 axis.

机构信息

Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, China.

Pathology Tissue Bank, Qilu Hospital of Shandong University, Jinan, China.

出版信息

Cell Death Dis. 2022 Sep 8;13(9):776. doi: 10.1038/s41419-022-05216-7.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f00a/9458743/b5e9169bc9ba/41419_2022_5216_Fig1_HTML.jpg

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