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MicroRNA-107 enhances radiosensitivity by suppressing granulin in PC-3 prostate cancer cells

Prostate cancer is the second leading cause of cancer-related death worldwide. Radiotherapy is often applied for the treatment, but radioresistance is a challenge in some patients. MicroRNAs have been reported to be involved in the DNA damage response induced by ionizing radiation and recent studies...

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Autores principales: Lo, Hua-Cheng, Hsu, Jia-Hao, Lai, Liang-Chuan, Tsai, Mong-Hsun, Chuang, Eric Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471693/
https://www.ncbi.nlm.nih.gov/pubmed/32883962
http://dx.doi.org/10.1038/s41598-020-71128-1
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author Lo, Hua-Cheng
Hsu, Jia-Hao
Lai, Liang-Chuan
Tsai, Mong-Hsun
Chuang, Eric Y.
author_facet Lo, Hua-Cheng
Hsu, Jia-Hao
Lai, Liang-Chuan
Tsai, Mong-Hsun
Chuang, Eric Y.
author_sort Lo, Hua-Cheng
collection PubMed
description Prostate cancer is the second leading cause of cancer-related death worldwide. Radiotherapy is often applied for the treatment, but radioresistance is a challenge in some patients. MicroRNAs have been reported to be involved in the DNA damage response induced by ionizing radiation and recent studies have reported microRNA-mediated radiosensitivity. In the present study, we found microRNA-107 (miR-107) enhanced radiosensitivity by regulating granulin (GRN) in prostate cancer (PC-3) cells. MiR-107 was downregulated and GRN was upregulated in response to ionizing radiation in PC-3 cells. Overexpression of miR-107 and knockdown of GRN promoted the sensitivity of PC3 cells to ionizing radiation. By rescue experiments of GRN, we revealed that radiosensitivity enhanced by miR-107 can be attenuated by GRN overexpression in PC-3 cells. Furthermore, we showed miR-107 enhanced radiation-induced G1/S phase arrest and G2/M phase transit, and identify delayed apoptosis by suppressing p21 and phosphorylation of CHK2. Collectively, these results highlight an unrecognized mechanism of miR-107-mediated GRN regulation in response to ionizing radiation and may advance therapeutic strategies for the treatment of prostate cancer.
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spelling pubmed-74716932020-09-04 MicroRNA-107 enhances radiosensitivity by suppressing granulin in PC-3 prostate cancer cells Lo, Hua-Cheng Hsu, Jia-Hao Lai, Liang-Chuan Tsai, Mong-Hsun Chuang, Eric Y. Sci Rep Article Prostate cancer is the second leading cause of cancer-related death worldwide. Radiotherapy is often applied for the treatment, but radioresistance is a challenge in some patients. MicroRNAs have been reported to be involved in the DNA damage response induced by ionizing radiation and recent studies have reported microRNA-mediated radiosensitivity. In the present study, we found microRNA-107 (miR-107) enhanced radiosensitivity by regulating granulin (GRN) in prostate cancer (PC-3) cells. MiR-107 was downregulated and GRN was upregulated in response to ionizing radiation in PC-3 cells. Overexpression of miR-107 and knockdown of GRN promoted the sensitivity of PC3 cells to ionizing radiation. By rescue experiments of GRN, we revealed that radiosensitivity enhanced by miR-107 can be attenuated by GRN overexpression in PC-3 cells. Furthermore, we showed miR-107 enhanced radiation-induced G1/S phase arrest and G2/M phase transit, and identify delayed apoptosis by suppressing p21 and phosphorylation of CHK2. Collectively, these results highlight an unrecognized mechanism of miR-107-mediated GRN regulation in response to ionizing radiation and may advance therapeutic strategies for the treatment of prostate cancer. Nature Publishing Group UK 2020-09-03 /pmc/articles/PMC7471693/ /pubmed/32883962 http://dx.doi.org/10.1038/s41598-020-71128-1 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lo, Hua-Cheng
Hsu, Jia-Hao
Lai, Liang-Chuan
Tsai, Mong-Hsun
Chuang, Eric Y.
MicroRNA-107 enhances radiosensitivity by suppressing granulin in PC-3 prostate cancer cells
title MicroRNA-107 enhances radiosensitivity by suppressing granulin in PC-3 prostate cancer cells
title_full MicroRNA-107 enhances radiosensitivity by suppressing granulin in PC-3 prostate cancer cells
title_fullStr MicroRNA-107 enhances radiosensitivity by suppressing granulin in PC-3 prostate cancer cells
title_full_unstemmed MicroRNA-107 enhances radiosensitivity by suppressing granulin in PC-3 prostate cancer cells
title_short MicroRNA-107 enhances radiosensitivity by suppressing granulin in PC-3 prostate cancer cells
title_sort microrna-107 enhances radiosensitivity by suppressing granulin in pc-3 prostate cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471693/
https://www.ncbi.nlm.nih.gov/pubmed/32883962
http://dx.doi.org/10.1038/s41598-020-71128-1
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