MicroRNA-21 inhibits mitochondria-mediated apoptosis in keloid
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Hao Wu1,*, Jie Wang1,*, Hui Ma2,*, Zhibo Xiao1 and Xiaoqun Dong3
1Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
2Department of Orthopaedics, The First Affiliated Hospital of General Hospital of The People's Liberation Army, Beijing, China
3Department of Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
*These authors have contributed equally to this work
Zhibo Xiao, email: [email protected]
Xiaoqun Dong, email: [email protected]
Keywords: microRNA-21, mitochondria, apoptosis, keloid, fibroblasts
Received: July 25, 2017 Accepted: August 28, 2017 Published: October 06, 2017
MicroRNA-21 acts as an oncogene by promoting cell proliferation and migration, whereas inhibiting apoptosis in majority of cancers. MicroRNA-21 is upregulated in human keloid fibroblasts. We hypothesized that microRNA-21 may contribute to pathogenesis of keloid fibroblasts. First, enhanced miR-21 but reduced mitochondrial-mediated apoptosis observed in keloid tissues indicated its importance in keloids development. Second, upregulation of microRNA-21 induced a decrease in the ratio of BAX to BCL-2 and suppressed mitochondrial fission in keloid fibroblasts. Third, by attenuating the decline in cellular mitochondrial membrane potential, overexpression of miR-21 suppressed cytochrome c release to the cytoplasm, followed by a decrease in the activity of intracellular caspase-9 and caspase-3, suggesting that mitochondrial-mediated proapoptotic pathway was impaired. Simultaneously, intracellular reactive oxygen species were decreased, indicating microRNA-21 undermined oxidative stress. This phenotype was reversed by miR-21 inhibition. Therefore, our study demonstrates that inhibition of microRNA-21 induces mitochondrial-mediated apoptosis in keloid fibroblasts, proposing microRNA-21 as a potential therapeutic target in keloid fibroblasts.
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