| Autor: |
Degli Esposti D; Epigenetics Group. International Agency for Research on Cancer (IARC), 150 Cours Albert-Thomas, 69008, Lyon, France., Aushev VN; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States of America., Lee E; Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, New York, NY, 10029, United States of America., Cros MP; Epigenetics Group. International Agency for Research on Cancer (IARC), 150 Cours Albert-Thomas, 69008, Lyon, France., Zhu J; Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, New York, NY, 10029, United States of America., Herceg Z; Epigenetics Group. International Agency for Research on Cancer (IARC), 150 Cours Albert-Thomas, 69008, Lyon, France., Chen J; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States of America. jia.chen@mssm.edu.; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States of America. jia.chen@mssm.edu.; Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States of America. jia.chen@mssm.edu.; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States of America. jia.chen@mssm.edu., Hernandez-Vargas H; Epigenetics Group. International Agency for Research on Cancer (IARC), 150 Cours Albert-Thomas, 69008, Lyon, France. vargash@iarc.fr. |
| Abstrakt: |
MicroRNAs (miRNAs) are small regulatory non-coding RNAs with a diversity of cellular functions, and are frequently dysregulated in cancer. Using a novel computational method (ActMir) that we recently developed, the "activity" of miRNA hsa-miR-500a was implicated in estrogen receptor (ER) positive breast cancer; however its targets and functional impact remain poorly understood. Here, we performed an extensive gene expression analysis in ER+ breast cancer cell lines, to reveal the targets of miR-500a-5p after experimental modulation of its levels. We found that among mRNAs targeted by miR-500a-5p there was enrichment in oxidative stress response genes. Moreover, in vitro exposure to oxidative stress using H 2 O 2 induces miR-500a-5p overexpression and downregulation of the oxidative stress targets TXNRD1 and NFE2L2. Finally, expression of several of the identified miR-500a-5p targets related to oxidative stress, including TXNRD1, was associated with ER+ breast cancer survival in multiple datasets. Overall, we identify miR-500a-5p as an oxidative stress response miRNA whose activity may define breast cancer progression and survival. |
