10.3389/fonc.2018.00199.s002 Sabrina Piras Sabrina Piras Anna L. Furfaro Anna L. Furfaro Rocco Caggiano Rocco Caggiano Lorenzo Brondolo Lorenzo Brondolo Silvano Garibaldi Silvano Garibaldi Caterina Ivaldo Caterina Ivaldo Umberto M. Marinari Umberto M. Marinari Maria A. Pronzato Maria A. Pronzato Raffaella Faraonio Raffaella Faraonio Mariapaola Nitti Mariapaola Nitti image_1_microRNA-494 Favors HO-1 Expression in Neuroblastoma Cells Exposed to Oxidative Stress in a Bach1-Independent Way.PDF Frontiers 2018 heme oxygenase 1 neuroblastoma miR-494 oxidative stress Bach1 2018-06-13 04:17:28 Figure https://frontiersin.figshare.com/articles/figure/image_1_microRNA-494_Favors_HO-1_Expression_in_Neuroblastoma_Cells_Exposed_to_Oxidative_Stress_in_a_Bach1-Independent_Way_PDF/6505364 <p>Heme oxygenase 1 (HO-1) is crucially involved in cell adaptation to oxidative stress and has been demonstrated to play an important role in cancer progression and resistance to therapies. We recently highlighted that undifferentiated neuroblastoma (NB) cells are prone to counteract oxidative stress through the induction of HO-1. Conversely, differentiated NB cells were more sensitive to oxidative stress since HO-1 was scarcely upregulated. In this work, we investigated the role played by miR-494, which has been proved to be involved in cancer biology and in the modulation of oxidative stress, in the upregulation of HO-1. We showed that NB differentiation downregulates miR-494 level. In addition, endogenous miR-494 inhibition in undifferentiated cells impairs HO-1 induction in response to exposure to 500 µM H<sub>2</sub>O<sub>2</sub>, reducing the number of viable cells. The analysis of Bach1 expression did not reveal any significant modifications in any experimental conditions tested, proving that the impairment of HO-1 induction observed in cells treated with miR-494 inhibitor and exposed to H<sub>2</sub>O<sub>2</sub> is independent from Bach1. Our results underline the role played by miR-494 in favoring HO-1 induction and cell adaptation to oxidative stress and contribute to the discovery of new potential pharmacological targets to improve anticancer therapies.</p>