MicroRNA-21 inhibits mitochondria-mediated apoptosis in keloid

// Hao Wu 1, * , Jie Wang 1, * , Hui Ma 2, * , Zhibo Xiao 1 and Xiaoqun Dong 3 1 Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China 2 Department of Orthopaedics, The First Affiliated Hospital of General Hospital of The People's Liberation Army, Beijing, China 3 Department of Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA * These authors have contributed equally to this work Correspondence to: Zhibo Xiao, email: xiaozhibodoctor@126.com Xiaoqun Dong, email: xiaoqun_dong@brown.edu Keywords: microRNA-21, mitochondria, apoptosis, keloid, fibroblasts Received: July 25, 2017      Accepted: August 28, 2017      Published: October 06, 2017 ABSTRACT 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.