Cortez, Maria Angelica
Calin, George A.
Giri, Dipak K.
Quini, Caio C.
Peltier, Heidi J.
Bader, Andreas G.
Heymach, John V.
Meyn, Raymond E.
Welsh, James W.
Total Authors: 15
 Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 - USA
 Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 - USA
 Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 - USA
 Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 - USA
 Sipaumdi Pathol Consultancy, Pearland, TX - USA
 Sao Paulo State Univ UNESP, Dept Phys & Biophys, Botucatu, SP - Brazil
 Mirna Therapeut Inc, Austin, TX - USA
 Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 - USA
Total Affiliations: 8
Web of Science Citations:
The microRNA (miR)-200s and their negative regulator ZEB1 have been extensively studied in the context of the epithelial mesenchymal transition. Loss of miR-200s has been shown to enhance cancer aggressiveness and metastasis, whereas replacement of miR-200 miRNAs has been shown to inhibit cell growth in several types of tumors, including lung cancer. Here, we reveal a novel function of miR-200c, a member of the miR-200 family, in regulating intracellular reactive oxygen species signaling and explore a potential application for its use in combination with therapies known to increase oxidative, stress such as radiation. We found that miR-200c overexpression increased cellular radiosensitivity by direct regulation of the oxidative stress response genes PRDX2, GAPB/Nrf2, and SESN1 in ways that inhibits DNA double-strand breaks repair, increase levels of reactive oxygen species, and upregulate p21. We used a lung cancer xenograft model to further demonstrate the therapeutic potential of systemic delivery of miR-200c to enhance radiosensitivity in lung cancer. Our findings suggest that the antitumor effects of miR-200c result partially from its regulation of the oxidative stress response; they further suggest that miR-200c, in combination with radiation, could represent a therapeutic strategy in the future. (AU)