MiR-485-3p and miR-485-5p suppress breast cancer cell metastasis by inhibiting PGC-1α expression.
MiR-485-3p and miR-485-5p suppress breast cancer cell metastasis by inhibiting PGC-1α expression.
复制标题
DOI：
10.1038/cddis.2016.27
复制
发表时间：
2016-03-24
影响因子：
9
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Lou C;Xiao M;Cheng S;Lu X;Jia S;Ren Y;Li Z
乳腺癌是全球女性癌症死亡的主要原因。大多数乳腺癌死亡是由于局部肿瘤的转移造成的。癌细胞通过将代谢物转移到合成代谢途径来支持其快速增殖，但在癌症转移期间，侵袭性癌细胞的增殖程序因迁移表型而暂停。在这项研究中，我们证明了两种成熟形式的 miRNA-485、miR-485-3p 和 miR-485-5p 通过直接靶向和抑制 PGC-1α 的表达来参与调节乳腺癌细胞中的线粒体呼吸、细胞迁移和细胞侵袭。具体而言，乳腺癌组织中miR-485-3p和miR-485-5p的表达水平均降低。 miR-485-3p和miR-485-5p的过表达抑制了线粒体呼吸以及体外细胞迁移和侵袭的潜力，并且还抑制了体内乳腺癌细胞的自发转移。 PGC-1α表达的恢复可以部分缓解线粒体呼吸和细胞侵袭的抑制。
Breast cancer is the worldwide leading cause of cancer mortality in women. The majority of deaths from breast cancer arise from metastasis of local tumors. Cancer cells support their rapid proliferation by diverting metabolites into anabolic pathways, but during cancer metastasis, the proliferative program of invasive cancer cells is suspended for a migratory phenotype. In this study, we demonstrated that both mature forms of miRNA-485, miR-485-3p and miR-485-5p were involved in regulating mitochondrial respiration, cell migration and cell invasion in breast cancer cells by directly targeting and inhibiting the expression of PGC-1α. Specifically, the expression levels of both miR-485-3p and miR-485-5p were decreased in breast cancer tissues. Overexpression of miR-485-3p and miR-485-5p suppressed mitochondrial respiration and potential for cell migration and invasion in vitro, and also inhibited spontaneous metastasis of breast cancer cells in vivo. The suppression of mitochondrial respiration and cell invasion could be partially relieved by restoration of PGC-1α expression.