title: miR-9 and let-7g enhance the sensitivity to ionizing radiation by suppression of NFκB1.
abstract: The activation of nuclear factor-kappa B1 (NFkB1) in cancer cells may confer resistance to ionizing radiation (IR). To enhance the therapeutic efficiency of IR in lung cancer, we screened for microRNAs (miRNAs) that suppress NFkB1 and observed their effects on radiosensitivity in a human lung cancer cell line. From time series data of miRNA expression in γ-irradiated H1299 human lung cancer cells, we found that the expression of miR-9 was inversely correlated with that of NFκB1. Overexpression of miR-9 down-regulated the level of NFκB1 in H1299 cells, and the surviving fraction of γ-irradiated cells was decreased. Interestingly, let-7g also suppressed the expression of NFκB1, although there was no canonical target site for let-7g in the NFκB1 3' untranslated region. From these results, we conclude that the expression of miR-9 and let-7g could enhance the efficiency of radiotherapy for lung cancer treatment through the inhibition of NFκB1.
authors.affiliation: Laboratory of Molecular and Genomic Medicine, Department of Biomedical Sciences, Seoul National University College of Medicine, Korea.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Arora
authors.forename: Rehana
authors.initials: R
authors.lastname: Qureshi
authors.forename: Shunzi
authors.initials: S
authors.lastname: Jin
authors.forename: Ae Kyoung
authors.initials: AK
authors.lastname: Park
authors.forename: Woong Yang
authors.initials: WY
authors.lastname: Park
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics*; D011839:Radiation, Ionizing; D016415:Sequence Alignment
chemical_list: C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; C487931:mirnlet7 microRNA, human