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Effects of HERV-R env Knockdown in Combination with Ionizing Radiation on Apoptosis-Related Gene Expression in A549 Lung Cancer Cells

Ja-Rang Lee, Yi-Deun Jung, Young-Hyun Kim, Sang-Je Park, Jae-Won Huh and Heui-Soo Kim

Radiotherapy has played a key role in the management of non–small-cell lung cancer (NSCLC). However, the use of radiotherapy in treating NSCLC is limited because of the intrinsic radiation resistance of tumor cells and injury to adjacent normal tissues. Many oncogenes are reported to be involved in radioresistance. Thus, novel moleculartargeting approaches to enhance the radiosensitivity of NSCLC cells are required to improve the therapeutic efficiency of radiotherapy. In this study, we report that expression of the human endogenous retrovirus-R (HERV-R) env gene is greatly elevated in γ-irradiation resistant A549 cells compared with radiation sensitive H460 cells. In addition, the HERV-R env gene was significantly increased in A549 cells after treatment with γ-irradiation. HERV-R env knockdown by siRNA in irradiated A549 cells led to overexpression of TP53 mRNA, followed by significant elevation in the levels of CDKN1A mRNA. Moreover, the expression of the apoptosis-related FAS-1 gene was increased, whereas the expression levels of the anti-apoptotic gene BCL2 were significantly decreased in the A549 cells in which the HERV-R env was suppressed by γ-irradiation. These results suggest that knockdown of HERV-R env with γ-irradiation causes cell cycle disturbances, which in turn induces apoptosis. In conclusion, the combination of HERV-R env knockdown and γ-irradiation has the potential to improve the therapeutic efficiency of radiotherapy for NSCLC.