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Communication

PTEN, A Target of Microrna-374b, Contributes to the Radiosensitivity of Canine Oral Melanoma Cells

1
Laboratory of Veterinary Radiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku Ourai Kita, Izumisano-shi, Osaka 598-8531, Japan
2
Veterinary Medical Center, Osaka Prefecture University, 1-58 Rinku Ourai Kita, Izumisano-shi, Osaka 598-8531, Japan
3
Laboratory of Veterinary Clinical Oncology, Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1112, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(18), 4631; https://doi.org/10.3390/ijms20184631
Received: 31 August 2019 / Revised: 15 September 2019 / Accepted: 16 September 2019 / Published: 18 September 2019
(This article belongs to the Section Molecular Oncology)
Canine oral malignant melanoma (CoMM) is often treated by radiation therapy in veterinary medicine. However, not all cases are successfully managed by this treatment. For improved efficacy of radiation therapy, biomarkers predicting the radiosensitivity of melanoma cells need to be explored. Here, we, first, developed the radioresistant CoMM cell line, KMeC/R. We found that the expression level of phosphatase and tensin homolog (PTEN) of KMeC/R cells was significantly downregulated compared with KMeC cells. Overexpression of PTEN successfully restored the radiosensitivity of KMeC/R cells, and silencing of PTEN significantly increased the radioresistance of the CoMM cells tested. Next, we focused on microRNAs (miRNAs) to explore the mechanisms of downregulation of PTEN in KMeC/R cells. miR-374b was upregulated in KMeC/R cells compared with that in KMeC cells and in the irradiated CoMM cells tested. Furthermore, miR-374b directly targeted PTEN based on the luciferase activity assay. Moreover, the extrinsic miR-374b significantly increased the radioresistance of KMeC cells. In addition, the expression level of PTEN was significantly downregulated and that of miR-374b tended to be upregulated in recurrent CoMM tissues after radiation therapy compared with the pre-treatment tissues. Thus, the current study suggested that the miR-374b/PTEN signaling pathway possibly plays an important role in CoMM radiosensitivity. View Full-Text
Keywords: dog; melanoma; miR-374b; PTEN; radiation therapy dog; melanoma; miR-374b; PTEN; radiation therapy
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MDPI and ACS Style

Noguchi, S.; Ogusu, R.; Wada, Y.; Matsuyama, S.; Mori, T. PTEN, A Target of Microrna-374b, Contributes to the Radiosensitivity of Canine Oral Melanoma Cells. Int. J. Mol. Sci. 2019, 20, 4631. https://doi.org/10.3390/ijms20184631

AMA Style

Noguchi S, Ogusu R, Wada Y, Matsuyama S, Mori T. PTEN, A Target of Microrna-374b, Contributes to the Radiosensitivity of Canine Oral Melanoma Cells. International Journal of Molecular Sciences. 2019; 20(18):4631. https://doi.org/10.3390/ijms20184631

Chicago/Turabian Style

Noguchi, Shunsuke, Ryo Ogusu, Yusuke Wada, Satoshi Matsuyama, and Takashi Mori. 2019. "PTEN, A Target of Microrna-374b, Contributes to the Radiosensitivity of Canine Oral Melanoma Cells" International Journal of Molecular Sciences 20, no. 18: 4631. https://doi.org/10.3390/ijms20184631

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