Zhang Di, Liu Xiaofeng, Li Yun, Sun Li, Liu Shu-Shu, Ma Yue, Zhang Huan, Wang Xin, Yu Yue
The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.
Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
Mol Ther Nucleic Acids. 2021 Jun 24;25:455-467. doi: 10.1016/j.omtn.2021.06.007. eCollection 2021 Sep 3.
Non-coding RNAs play essential roles in breast cancer progression by regulating proliferation, differentiation, invasion, and metastasis. However, our understanding of most microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in breast cancer is still limited. miR-586 has been identified as an important factor in the progression of some types of cancer, but its exact function and relative regulation mechanisms in breast cancer development need to be further investigated. In this study, we showed miR-586 functioned as an oncogene by promoting breast cancer proliferation and metastasis both and . Meanwhile, miR-586 induced Wnt/β-catenin activation by directly targeting Wnt/β-catenin signaling antagonists SFRP1 and DKK2/3. Moreover, we demonstrated that LINC01189 functioned as a tumor suppressor and inhibited breast cancer progression through inhibiting an epithelial-mesenchymal transition (EMT)-like phenotype by sponging miR-586. In addition, β-catenin/TCF4 transactivated ZEB1, resulting in a transcriptional repression of LINC01189 expression. In conclusion, our data uncovered the LINC01189-miR-586-ZEB1 feedback loop and provided a novel mechanism participating in the regulation of Wnt/β-catenin signaling in breast cancer progression.
非编码RNA通过调节增殖、分化、侵袭和转移在乳腺癌进展中发挥重要作用。然而,我们对乳腺癌中大多数微小RNA(miRNA)和长链非编码RNA(lncRNA)的了解仍然有限。miR-586已被确定为某些类型癌症进展中的一个重要因素,但其在乳腺癌发展中的确切功能和相关调控机制仍需进一步研究。在本研究中,我们表明miR-586通过促进乳腺癌的增殖和转移而发挥癌基因的作用。同时,miR-586通过直接靶向Wnt/β-连环蛋白信号拮抗剂SFRP1和DKK2/3诱导Wnt/β-连环蛋白激活。此外,我们证明LINC01189作为一种肿瘤抑制因子,通过海绵吸附miR-586抑制上皮-间质转化(EMT)样表型,从而抑制乳腺癌进展。此外,β-连环蛋白/TCF4反式激活ZEB1,导致LINC01189表达的转录抑制。总之,我们的数据揭示了LINC01189-miR-586-ZEB1反馈环,并提供了一种参与调节乳腺癌进展中Wnt/β-连环蛋白信号的新机制。