Zhang Guoqiang, Liu Zengyan, Cui Guanghe, Wang Xiaohong, Yang Zhenlin
Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, 256603, China.
Tumour Biol. 2014 Nov;35(11):11137-45. doi: 10.1007/s13277-014-2412-0. Epub 2014 Aug 8.
MicroRNAs (miRNAs) are emerging as critical regulators in carcinogenesis and tumor progression. Recently, miR-486-5p has been proved to play an important role in several cancers, but its functions in the context of breast cancer (BC) remain unknown. In this study, we found that miR-486-5p expression is significantly downregulated in BC tissues and cell lines. Overexpression of miR-486-5p dramatically suppressed BC cell proliferation in vitro and in vivo, induced G0/G1 arrest, and promoted apoptosis. We subsequently identified the oncogene PIM-1 as a direct target of miR-486-5p in BC. Overexpression of PIM-1 attenuated the function of miR-486-5p in BC cells. Together, we conclude that miR-486-5p exerts its antiproliferative function by directly downregulating PIM-1 expression. This novel miR-486-5p/PIM-1 axis provides insight into the pathogenesis of BC and might be therapeutic targets for prevention or treatment of BC.
微小RNA(miRNA)正逐渐成为癌症发生和肿瘤进展中的关键调节因子。最近,miR-486-5p已被证明在多种癌症中发挥重要作用,但其在乳腺癌(BC)中的功能仍不清楚。在本研究中,我们发现miR-486-5p在BC组织和细胞系中的表达显著下调。miR-486-5p的过表达在体外和体内均显著抑制BC细胞增殖,诱导G0/G1期阻滞,并促进细胞凋亡。我们随后确定癌基因PIM-1是BC中miR-486-5p的直接靶点。PIM-1的过表达减弱了miR-486-5p在BC细胞中的功能。我们共同得出结论,miR-486-5p通过直接下调PIM-1表达发挥其抗增殖功能。这个新的miR-486-5p/PIM-1轴为BC的发病机制提供了见解,可能是预防或治疗BC的治疗靶点。