Reproductive Medicine Center, Jinhua People's Hospital, Jinhua 321000, Zhejiang, China; Zhejiang Normal University, Jinhua People's Hospital Joint Center for Biomedical Research, Jinhua 321000, Zhejiang, China.
Reproductive Medicine Center, Jinhua People's Hospital, Jinhua 321000, Zhejiang, China.
Gene. 2019 Jan 30;683:47-53. doi: 10.1016/j.gene.2018.10.014. Epub 2018 Oct 6.
Breast cancer is one of the most common malignant tumors among females. Recent studies demonstrated that microRNAs (miRNAs) played an important role in the regulation of tumor progression. In our present study, we firstly detected miR-340-5p expression in breast cancer cell lines and found lower expression of miR-340-5p in breast cancer cell lines (MCF-7, MDA-MB-231, BT-549, ZR-75-1) through qRT-PCR. Overexpressed miR-340-5p inhibited cell proliferation and drug resistance to docetaxel with enhanced cell apoptosis of breast cancer cells. Through bioinformatic prediction, we found that LGR5 was a potential target of miR-340-5p. LGR5 was highly expressed in breast cancer cells. Relative expression of LGR5 was negatively regulated by miR-340-5p. Knockdown of LGR5 also inhibited cell proliferation and drug resistance to docetaxel with enhanced cell apoptosis of breast cancer cells. Moreover, knockdown of LGR5 decreased the expression of β-catenin, c-myc, Survivin. The activation of Wnt/β-catenin pathway contracted the effects of LGR5 siRNA, indicating that LGR5 siRNA inhibited cell proliferation and drug resistance with induced apoptosis via suppressing Wnt/β-catenin signaling pathway in breast cancer. Taken together, our study demonstrated that overexpressed miR-340-5p inhibited cell proliferation and drug resistance with increased apoptosis of breast cancer cells through down-regulating LGR5 expression via Wnt/β-catenin pathway. The miR-340-5p/LGR5 axis may provide a new perspective for treatment for breast cancer.
乳腺癌是女性中最常见的恶性肿瘤之一。最近的研究表明，microRNAs（miRNAs）在肿瘤进展的调控中发挥着重要作用。在我们目前的研究中，我们首先检测了乳腺癌细胞系中的 miR-340-5p 表达，通过 qRT-PCR 发现 miR-340-5p 在乳腺癌细胞系（MCF-7、MDA-MB-231、BT-549、ZR-75-1）中表达较低。过表达 miR-340-5p 抑制乳腺癌细胞的增殖和对多西紫杉醇的耐药性，并增强细胞凋亡。通过生物信息学预测，我们发现 LGR5 是 miR-340-5p 的一个潜在靶点。LGR5 在乳腺癌细胞中高表达。LGR5 的相对表达受 miR-340-5p 的负调控。LGR5 的敲低也抑制了乳腺癌细胞的增殖和对多西紫杉醇的耐药性，并增强了细胞凋亡。此外，LGR5 的敲低降低了β-catenin、c-myc、Survivin 的表达。Wnt/β-catenin 通路的激活减弱了 LGR5 siRNA 的作用，表明 LGR5 siRNA 通过抑制 Wnt/β-catenin 信号通路抑制乳腺癌细胞的增殖和耐药性，诱导细胞凋亡。总之，我们的研究表明，过表达 miR-340-5p 通过下调 LGR5 表达，通过 Wnt/β-catenin 通路抑制乳腺癌细胞的增殖和耐药性，增加细胞凋亡。miR-340-5p/LGR5 轴可能为乳腺癌的治疗提供新的视角。
