Ma Lin, Ma Shan, Zhao Guimei, Yang Longqiu, Zhang Peng, Yi Qingting, Cheng Shuguang
Department of Neurology, Shanghai Tongji Hospital, Tongji University, School of Medicine, Shanghai, 200065, China.
Department of Oncology, The Center Hospital of Zaozhuang Mining Group, Zaozhuang, 277000, China.
Cancer Med. 2016 Apr;5(4):684-92. doi: 10.1002/cam4.623. Epub 2016 Feb 2.
Breast cancer is one of the most common malignant tumors in women worldwide. The microRNAs (miRNAs) are small, noncoding RNAs that regulate various biological processes, including breast cancer. miR-708 played an important role in a variety of cancers. However, its involvement in breast cancer remains largely unclear. In this study, we found that forced the expression of miR-708 in breast cancer cell lines decreased cell proliferation and invasion, whereas inhibition of miR-708 increased cell growth and invasion. miR-708 could directly target the LSD1 3'UTR to downregulate the expression. Further studies suggested that inhibition of LSD1 could phenocopied function of the miR-708 overexpression in MDA-MB-231 cells .Overexpression of LSD1 could counteract the effects of miR-708 on the proliferation and invasion. Taken together, the results indicate that miR-708 may function as a tumor suppressor gene in breast cancer development, and miR-708/LSD1 axis may be a therapeutic intervention in breast cancer in the future.
乳腺癌是全球女性中最常见的恶性肿瘤之一。微小RNA（miRNA）是一类小的非编码RNA，可调节包括乳腺癌在内的各种生物学过程。miR-708在多种癌症中发挥重要作用。然而，其在乳腺癌中的作用在很大程度上仍不清楚。在本研究中，我们发现，在乳腺癌细胞系中强制表达miR-708可降低细胞增殖和侵袭能力，而抑制miR-708则可增加细胞生长和侵袭能力。miR-708可直接靶向赖氨酸特异性去甲基化酶1（LSD1）的3'非翻译区（3'UTR）以下调其表达。进一步研究表明，抑制LSD1可模拟miR-708在MDA-MB-231细胞中过表达的功能。LSD1的过表达可抵消miR-708对增殖和侵袭的影响。综上所述，结果表明miR-708在乳腺癌发生发展过程中可能作为一种肿瘤抑制基因发挥作用，且miR-708/LSD1轴可能成为未来乳腺癌治疗的一个干预靶点。
