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miR-23b-3p 通过重编程代谢促进骨肉瘤中 PGC1α 的增殖。

miR-23b-3p suppressing PGC1α promotes proliferation through reprogramming metabolism in osteosarcoma.

机构信息

Department of Rehabilitation Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Department of Rehabilitation Medicine, Putuo People's Hospital Affiliated to Tongji University, Shanghai, China.

出版信息

Cell Death Dis. 2019 May 16;10(6):381. doi: 10.1038/s41419-019-1614-1.

Abstract

Metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis is a hallmark of osteosarcoma (OS). However, the mechanisms of the metabolic switch have not been completely elucidated. Here we reported that the miR-23b-3p was significantly upregulated in OS cells. Functional studies suggested that knockdown of miR-23b-3p could inhibit OS cell proliferation in vitro or in vivo. In addition, suppression of miR-23b-3p could lead to upregulation of OXPHOS and suppression of glycolysis. Mechanistically, miR-23b-3p promoted OS cell proliferation and inhibited OXPHOS in OS, at least in part, by directly targeting peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α) and inhibiting its expression. Our data highlights important roles of miR-23b-3p and PGC1α in glucose metabolism reprogram of OS. The suppression of miR-23b-3p may provide effective therapeutic strategies for the treatment of OS.

摘要

代谢从氧化磷酸化 (OXPHOS) 向糖酵解的转变是骨肉瘤 (OS) 的一个标志。然而,代谢转换的机制尚未完全阐明。在这里,我们报道 miR-23b-3p 在 OS 细胞中显著上调。功能研究表明,miR-23b-3p 的敲低可以抑制 OS 细胞在体外或体内的增殖。此外,抑制 miR-23b-3p 可以导致 OXPHOS 的上调和糖酵解的抑制。在机制上,miR-23b-3p 通过直接靶向过氧化物酶体增殖物激活受体 γ 共激活因子 1α (PGC1α) 并抑制其表达,促进 OS 细胞增殖并抑制 OS 中的 OXPHOS。我们的数据强调了 miR-23b-3p 和 PGC1α 在 OS 葡萄糖代谢重编程中的重要作用。抑制 miR-23b-3p 可能为 OS 的治疗提供有效的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7af4/6522531/b32d2e6b0378/41419_2019_1614_Fig1_HTML.jpg

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