Department of Breast Surgery, the First Affiliated Hospital of Zhengzhou University, No.1 Jianshedong Road, Erqi District, Zhengzhou, Henan Province, People's Republic of China.
Cell Death Dis. 2021 Apr 19;12(5):412. doi: 10.1038/s41419-021-03684-x.
An increasing amount of evidence has proven the vital role of circular RNAs (circRNAs) in cancer progression. However, there remains a dearth of knowledge on the function of circRNAs in triple-negative breast cancer (TNBC). Utilizing a circRNA microarray dataset, four circRNAs were identified to be abnormally expressed in TNBC. Among them, circBACH2 was most significantly elevated in TNBC cancerous tissues and its high expression was positively correlated to the malignant progression of TNBC patients. In normal human mammary gland cell line, the overexpression of circBACH2 facilitated epithelial to mesenchymal transition and cell proliferation. In TNBC cell lines, circBACH2 knockdown suppressed the malignant progression of TNBC cells. Mechanistically, circBACH2 sponged miR-186-5p and miR-548c-3p, thus releasing the C-X-C chemokine receptor type 4 (CXCR4) expression. The interference of miR-186-5p/miR-548c-3p efficiently promoted the cell proliferation, migration, and invasion suppressed by circBACH2 knockdown in the TNBC cell lines. Finally, circBACH2 knockdown repressed the growth and lung metastasis of TNBC xenografts in nude mice. In summary, circBACH2 functions as an oncogenic circRNA in TNBC through a novel miR-186-5p/miR-548c-3p/CXCR4 axis.
越来越多的证据证明了环状 RNA（circRNAs）在癌症进展中的重要作用。然而，关于 circRNAs 在三阴性乳腺癌（TNBC）中的功能仍然知之甚少。利用 circRNA 微阵列数据集，发现了四个在 TNBC 中异常表达的 circRNAs。其中，circBACH2 在 TNBC 癌组织中的表达水平升高最为显著，其高表达与 TNBC 患者的恶性进展呈正相关。在正常的人乳腺细胞系中，circBACH2 的过表达促进了上皮间质转化和细胞增殖。在 TNBC 细胞系中，circBACH2 的敲低抑制了 TNBC 细胞的恶性进展。机制上，circBACH2 作为海绵吸附 miR-186-5p 和 miR-548c-3p，从而释放 C-X-C 趋化因子受体 4（CXCR4）的表达。miR-186-5p/miR-548c-3p 的干扰有效地促进了 TNBC 细胞系中 circBACH2 敲低抑制的细胞增殖、迁移和侵袭。最后，circBACH2 的敲低抑制了裸鼠中 TNBC 异种移植的生长和肺转移。总之，circBACH2 通过一种新的 miR-186-5p/miR-548c-3p/CXCR4 轴在 TNBC 中发挥致癌 circRNA 的作用。
