Curcumin Promotes Osteosarcoma Cell Death by Activating miR-125a/ERR Signal Pathway

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.