Fu Xiaonan, Mao Xuan, Wang Yuxiang, Ding Xianfeng, Li Yongfeng
College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, P.R. China.
Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, P.R. China.
Oncol Rep. 2017 Sep;38(3):1851-1856. doi: 10.3892/or.2017.5839. Epub 2017 Jul 19.
In this study, we found that let-7c-5p expression was clearly downregulated in breast cancer tissues compared with that of corresponding adjacent tissues. Furthermore, overexpression of let-7c-5p in MCF-7 breast cancer cells could significantly inhibit cell proliferation and induce cell apoptosis. The target genes of let-7c-5p were predicted by the way of bioinformatics, and validated by dual luciferase reporter assay and western blotting demonstrating that excision repair cross complementing 6 (ERCC6) gene was a direct target. Collectively, the present study suggested that let-7c-5p acted as a tumor suppressor in breast cancer possibly by negatively regulating ERCC6, which took an important part in nucleotide excision repair and it may provide a new potential strategy for breast cancer therapy.
在本研究中,我们发现与相应的癌旁组织相比,let-7c-5p在乳腺癌组织中的表达明显下调。此外,在MCF-7乳腺癌细胞中过表达let-7c-5p可显著抑制细胞增殖并诱导细胞凋亡。通过生物信息学方法预测let-7c-5p的靶基因,并通过双荧光素酶报告基因检测和蛋白质印迹法进行验证,结果表明切除修复交叉互补6(ERCC6)基因是其直接靶标。总体而言,本研究提示let-7c-5p可能通过负向调节ERCC6在乳腺癌中发挥肿瘤抑制作用,ERCC6在核苷酸切除修复中起重要作用,这可能为乳腺癌治疗提供一种新的潜在策略。