Curcumin Promotes Osteosarcoma Cell Death by Activating miR-125a/ERR Signal Pathway
Curcumin Promotes Osteosarcoma Cell Death by Activating miR-125a/ERR Signal Pathway
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DOI：
10.1002/jcb.25612
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发表时间：
2017-01-01
影响因子：
4
通讯作者：
Wang, Junjian
中科院分区：
文献类型：
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作者：
Chen, Peng;Wang, Haibin;Wang, Junjian
姜黄素对包括骨肉瘤在内的多种人类癌症显示出有价值的治疗潜力。然而，其抗肿瘤作用的分子机制尚不清楚。通过RNA序列分析，我们发现姜黄素显著下调骨肉瘤细胞雌激素相关受体α(ERR)的表达。过表达ERR可减少姜黄素诱导的细胞死亡，清除姜黄素诱导的活性氧(ROS)，同时沉默ERR可使骨肉瘤细胞对姜黄素敏感，导致细胞增殖受抑。此外，我们还发现姜黄素通过上调miR-125a的表达来抑制ERR基因的表达。这项研究的数据揭示了姜黄素介导的细胞凋亡的一种新机制，即通过激活miR-125a/ERR途径杀死肿瘤细胞。我们的研究也为单独靶向ERR或联合姜黄素治疗骨肉瘤提供了进一步的支持。J.细胞。生物化学。2017年，118：74-81。(C)2016威利期刊公司。
Curcumin has demonstrated valuable therapeutic potential against a variety of human cancers including osteosarcoma. However, the molecular mechanisms underlying its anti-tumor effect remain to be poorly understood. By RNA sequence profiling, we found that curcumin significantly down-regulates the expression of estrogen-related receptor alpha (ERR) in osteosarcoma cells. Overexpression of ERR diminished curcumin-activated apoptotic cell death and scavenged curcumin-induced reactive oxygen species (ROS), while ERR silencing sensitized osteosarcoma cells to curcumin, resulting in increased inhibition of cell proliferation. In addition, we found that curcumin suppressed the ERR gene expression through upregulation of miR-125a. Data from this study revealed a novel mechanism for curcumin-mediated apoptotic cell death, which involves tumor cell killing via activating miR-125a/ERR pathway. Our studies also provide further support for osteosarcoma therapy by targeting ERR alone or in combination with curcumin. J. Cell. Biochem. 118: 74-81, 2017. (c) 2016 Wiley Periodicals, Inc.