Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou 221009, China.
Department of Breast Surgery, Xuzhou Central Hospital, Xuzhou 221009, China.
Biochem Biophys Res Commun. 2018 Jul 20;502(3):358-363. doi: 10.1016/j.bbrc.2018.05.166. Epub 2018 May 31.
As the development of sequencing technology, more and more circular RNAs (circRNAs) are identified in human cancer tissues. Increasing evidences imply circRNAs are important regulators in tumor progression. Nevertheless, how circRNAs participate in breast cancer development and progression is not well understood. In the present study, we identified a novel circRNA hsa_circ_0008039 with upregulated expression level in breast cancer tissues. By functional experiments, we found that hsa_circ_0008039 depletion significantly suppressed the proliferation, arrested cell-cycle progression and reduced migration in breast cancer. Mechanistic investigations suggested that hsa_circ_0008039 served as a competing endogenous RNA (ceRNA) of miR-432-5p. Subsequently, E2F3 was identified as the functional target of miR-432-5p and overexpression of hsa_circ_0008039 elevated E2F3 expression in breast cancer. On the whole, our study indicated that hsa_circ_0008039 exerted oncogenic roles in breast cancer and suggested the hsa_circ_0008039/miR-432-5p/E2F3 axis might be a potential therapeutic target.
随着测序技术的发展，越来越多的环状 RNA（circRNAs）在人类癌症组织中被鉴定出来。越来越多的证据表明 circRNAs 是肿瘤进展中的重要调节因子。然而，circRNAs 如何参与乳腺癌的发生和发展还不是很清楚。在本研究中，我们鉴定了一种新型的环状 RNA hsa_circ_0008039，其在乳腺癌组织中表达上调。通过功能实验，我们发现 hsa_circ_0008039 的缺失显著抑制了乳腺癌细胞的增殖，细胞周期进程停滞，并减少了迁移。机制研究表明，hsa_circ_0008039 作为 miR-432-5p 的竞争性内源 RNA（ceRNA）。随后，鉴定出 E2F3 是 miR-432-5p 的功能性靶基因，hsa_circ_0008039 的过表达可上调乳腺癌中 E2F3 的表达。总的来说，我们的研究表明 hsa_circ_0008039 在乳腺癌中发挥致癌作用，并提示 hsa_circ_0008039/miR-432-5p/E2F3 轴可能是一个潜在的治疗靶点。
