Center of Diagnosis and Treatment of Breast Disease, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.
Department of General Surgery, Maternity and Child Care Hospital of Weifang, Weifang, People's Republic of China.
J Cell Physiol. 2019 Jul;234(7):10819-10826. doi: 10.1002/jcp.27906. Epub 2019 Jan 9.
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. The aim of our study was to investigate the functional role of microRNA-135b (miR-135b) in TNBC. A real-time polymerase chain reaction assay was used to quantify miR-135b expression levels in 90 paired TNBC tissue and adjacent normal tissue samples. Wound-healing and transwell assays were performed to evaluate the effects of miR-135b expression on the migration and invasion of TNBC cells. Luciferase reporter and western blot analyses were used to verify whether the mRNA encoding APC is a major target of miR-135b. In the current study, we found that miR-135b was highly expressed in TNBC tissue and cells, and the expression levels were correlated with lymph node status and TNM stage. In TNBC cells, the ectopic expression of miR-135b promoted cell proliferation and invasion in vitro. In addition, our study proved that the overexpression of miR-135b significantly suppressed APC expression by targeting the 3'-untranslated region of APC, whereas enhanced APC expression could partially abrogate the miR-135b-mediated promotion of carcinogenic traits in TNBC cells. Taken together, our study demonstrated that miR-135b expression promoted the proliferation and invasion of TNBC by downregulating APC expression, indicating that miR-135b may serve as a promising target for the treatment of TNBC patients.
三阴性乳腺癌(TNBC)是最具侵袭性的乳腺癌亚型。我们的研究旨在探讨 microRNA-135b(miR-135b)在 TNBC 中的功能作用。实时聚合酶链反应检测 90 对 TNBC 组织及其相邻正常组织样本中 miR-135b 的表达水平。划痕愈合和 Transwell 实验评估 miR-135b 表达对 TNBC 细胞迁移和侵袭的影响。荧光素酶报告和 Western blot 分析用于验证 APC 编码 mRNA 是否是 miR-135b 的主要靶标。在本研究中,我们发现 miR-135b 在 TNBC 组织和细胞中高表达,表达水平与淋巴结状态和 TNM 分期相关。在 TNBC 细胞中,miR-135b 的异位表达促进了体外细胞增殖和侵袭。此外,我们的研究证明,通过靶向 APC 的 3'-非翻译区,过表达 miR-135b 可显著抑制 APC 表达,而增强 APC 表达可部分阻断 miR-135b 介导的 TNBC 细胞致癌特征的促进作用。综上所述,我们的研究表明,miR-135b 通过下调 APC 表达促进 TNBC 的增殖和侵袭,表明 miR-135b 可能成为治疗 TNBC 患者的有前途的靶点。