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MiR-485-3p and miR-485-5p suppress breast cancer cell metastasis by inhibiting PGC-1α expression

机译:MiR-485-3p和miR-485-5p通过抑制PGC-1α表达来抑制乳腺癌细胞转移

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摘要

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.
机译:乳腺癌是女性癌症死亡的全球主要原因。乳腺癌的大部分死亡原因是局部肿瘤的转移。癌细胞通过将代谢物转移至合成代谢途径来支持其快速增殖,但是在癌症转移过程中,浸润性癌细胞的增殖程序因迁移表型而被暂停。在这项研究中,我们证明了miRNA-485,miR-485-3p和miR-485-5p的两种成熟形式均通过直接靶向和抑制MRNA的表达而参与调节乳腺癌细胞的线粒体呼吸,细胞迁移和细胞侵袭。 PGC-1α。具体而言,miR-485-3p和miR-485-5p的表达水平在乳腺癌组织中均降低。 miR-485-3p和miR-485-5p的过度表达抑制了线粒体呼吸作用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。恢复PGC-1α表达可以部分缓解线粒体呼吸抑制和细胞侵袭。

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