title: In Vivo Delivery of miR-34a Sensitizes Lung Tumors to Radiation Through RAD51 Regulation.
abstract: MiR-34a, an important tumor-suppressing microRNA, is downregulated in several types of cancer; loss of its expression has been linked with unfavorable clinical outcomes in non-small-cell lung cancer (NSCLC), among others. MiR-34a represses several key oncogenic proteins, and a synthetic mimic of miR-34a is currently being tested in a cancer trial. However, little is known about the potential role of miR-34a in regulating DNA damage response and repair. Here, we demonstrate that miR-34a directly binds to the 3' untranslated region of RAD51 and regulates homologous recombination, inhibiting double-strand-break repair in NSCLC cells. We further demonstrate the therapeutic potential of miR-34a delivery in combination with radiotherapy in mouse models of lung cancer. Collectively, our results suggest that administration of miR-34a in combination with radiotherapy may represent a novel strategy for treating NSCLC.
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Maria Angelica
authors.initials: MA
authors.lastname: Cortez
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: David
authors.initials: D
authors.lastname: Valdecanas
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Sharareh
authors.initials: S
authors.lastname: Niknam
authors.affiliation: Mirna Therapeutics, Inc., Austin, Texas, USA.
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Peltier
authors.affiliation: Department of Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Lixia
authors.initials: L
authors.lastname: Diao
authors.affiliation: Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Uma
authors.initials: U
authors.lastname: Giri
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Gomez
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Joe Y
authors.initials: JY
authors.lastname: Chang
authors.affiliation: Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: John Victor
authors.initials: JV
authors.lastname: Heymach
authors.affiliation: Mirna Therapeutics, Inc., Austin, Texas, USA.
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Bader
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: James William
authors.initials: JW
authors.lastname: Welsh