Title: miR-155 mediates arsenic trioxide resistance by activating Nrf2 and suppressing apoptosis in lung cancer cells.
Authors: Gu, Shiyan; Lai, Yanhao; Chen, Hongyu; Liu, Yuan; Zhang, Zunzhen
Published In Sci Rep, (2017 09 22)
Abstract: Arsenic trioxide (ATO) resistance is a challenging problem in chemotherapy. However, the underlying mechanisms remain to be elucidated. In this study, we identified a high level of expression of miR-155 in a human lung adenocarcinoma A549R cell line that is highly resistant to ATO. We showed that the high level of miR-155 was associated with increased levels of cell survival, colony formation, cell migration and decreased cellular apoptosis, and this was mediated by high levels of Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1) and a high ratio of Bcl-2/Bax. Overexpression of the miR-155 mimic in A549R cells resulted in increased levels of colony formation and cell migration as well as reduced apoptosis along with increased Nrf2, NQO1 and HO-1. In contrast, silencing of miR-155 expression with its inhibitor in the cells, significantly decreased the cellular levels of Nrf2, NQO1 and HO-1 as well as the ratio of Bcl-2/Bax. This subsequently reduced the level of colony formation and cell migration facilitating ATO-induced apoptosis. Our results indicate that miR-155 mediated ATO resistance by upregulating the Nrf2 signaling pathway, but downregulating cellular apoptosis in lung cancer cells. Our study provides new insights into miR-155-mediated ATO resistance in lung cancer cells.
PubMed ID: 28939896
MeSH Terms: Adenocarcinoma of Lung/drug therapy*; Adenocarcinoma of Lung/genetics; Adenocarcinoma of Lung/metabolism; Antineoplastic Agents/pharmacology*; Apoptosis/drug effects; Arsenic Trioxide/pharmacology*; Cell Line, Tumor; Drug Resistance, Neoplasm*; Humans; Lung Neoplasms/drug therapy*; Lung Neoplasms/genetics; Lung Neoplasms/metabolism; MicroRNAs/genetics*; MicroRNAs/metabolism; NF-E2-Related Factor 2/genetics*; NF-E2-Related Factor 2/metabolism; Signal Transduction/drug effects