Lou C, Xiao M, Cheng S, Lu X, Jia S, Ren Y, Li Z
Department of Breast Surgery, The Affiliated Tumor Hospital, Harbin Medical University, Harbin, China.
Cell Death Dis. 2016 Mar 24;7(3):e2159. doi: 10.1038/cddis.2016.27.
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.
乳腺癌是全球女性癌症死亡的主要原因。大多数乳腺癌死亡源于局部肿瘤的转移。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,但在癌症转移过程中,侵袭性癌细胞的增殖程序会暂停以形成迁移表型。在本研究中,我们证明了成熟形式的miRNA-485,即miR-485-3p和miR-485-5p,通过直接靶向并抑制PGC-1α的表达,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,miR-485-3p和miR-485-5p在乳腺癌组织中的表达水平均降低。miR-485-3p和miR-485-5p的过表达在体外抑制线粒体呼吸以及细胞迁移和侵袭的能力,并且在体内也抑制乳腺癌细胞的自发转移。通过恢复PGC-1α的表达,可部分缓解线粒体呼吸和细胞侵袭的抑制。