Japanese Journal of Veterinary Research;Volume 67 Number 2

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MicroRNA-205 enhances the radiosensitivity of canine oral melanoma cells by inhibiting E2F1

Wada, Yusuke;Noguchi, Shunsuke;Nishiyama, Yuki;Matsuyama, Satoshi;Mori, Takashi;Igase, Masaya;Mizuno, Takuya;Shimamura, Shunsuke;Shimada, Terumasa

Permalink : http://hdl.handle.net/2115/74796
JaLCDOI : 10.14943/jjvr.67.2.151
KEYWORDS : ATM;E2F1;melanoma;miR-205;radiation

Abstract

Canine oral malignant melanoma (CoMM) is a highly aggressive tumor associated with a poor survival due to both local disease progression and high metastatic potential. Radiotherapy is often applied as the treatment for dogs with melanoma. However, the therapeutic effect of it may be limited due to the relative radio-resistance. Recent studies have demonstrated that microRNAs (miRNAs) play an important role in radiosensitivity. However, little is known with regard to the association of radiosensitivity with miRNAs in canine melanoma cells. In the present study, we showed that miR-205, which is downregulated in CoMM tissues compared to its expression in normal oral tissues, promoted the radiosensitivity of canine melanoma cells. In addition, our results indicated that the enhancement of radiosensitivity by miR-205 resulted, at least in part, from negative regulation of E2 transcription factor 1 (E2F1)-ATM signaling, which finding was validated by using the methods of knockdown of E2F1 and knockout of ATM for CoMM cell lines. However, other mechanisms regulated by miR-205 were considered to contribute to radiosensitivity in cutaneous melanoma cells, because downregulation of E2F1 did not decrease the expression level of ATM. Taken together, these findings suggest that miR-205 plays a role in radiosensitivity of CoMM cells by inhibiting E2F1 and indicate that utilization of this miRNA as a radiosensitizing factor might be a new strategy for treatment of CoMM.

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