MicroRNA-130a modulates a radiosensitivity of rectal cancer by targeting SOX4
Radioresistance poses a major challenge in the treatment of advanced rectal cancer. Therefore, understanding the detailed mechanisms of radioresistance may improve patient response to irradiation and the survival rate. To identify the novel targets that modulate the radiosensitivity of rectal cancer...
Main Authors: | , , , |
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Format: | Article |
Language: | English |
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Elsevier
2019-09-01
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Series: | Neoplasia: An International Journal for Oncology Research |
Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558619301678 |
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author | Huyen Trang Ha Thi Hye-Yeon Kim Young-Mi Kim Suntaek Hong |
author_facet | Huyen Trang Ha Thi Hye-Yeon Kim Young-Mi Kim Suntaek Hong |
author_sort | Huyen Trang Ha Thi |
collection | DOAJ |
description | Radioresistance poses a major challenge in the treatment of advanced rectal cancer. Therefore, understanding the detailed mechanisms of radioresistance may improve patient response to irradiation and the survival rate. To identify the novel targets that modulate the radiosensitivity of rectal cancer, we performed small RNA sequencing with human rectal cancer cell lines. Through bioinformatics analysis, we selected microRNA-310a (miR-130a) as a promising candidate to elucidate radioresistance. miR-130a was dramatically upregulated in radiosensitive rectal cancer cells and overexpression of miR-130a promotes rectal cancer cell radiosensitivity. Mechanically, miR-130a reversed the epithelial-mesenchymal transition phenotype of rectal cancer cells following inhibition of cell invasion upon irradiation. Moreover, miR-130a also inhibited the repair of irradiation-induced DNA damage followed by cell death. We identified that SOX4 was a direct target of miR-130a. Overexpression of SOX4 reversed the promotion activity of miR-130a on radiosensitivity. Together, our findings suggest that miR-130a functions as a radiosensitizer in rectal cancer and reveals a potential therapeutic target and preoperative prognostic marker for radiotherapy. |
first_indexed | 2024-12-23T23:45:32Z |
format | Article |
id | doaj.art-e62215ef8abc42659513d3485e9832fc |
institution | Directory Open Access Journal |
issn | 1476-5586 |
language | English |
last_indexed | 2024-12-23T23:45:32Z |
publishDate | 2019-09-01 |
publisher | Elsevier |
record_format | Article |
series | Neoplasia: An International Journal for Oncology Research |
spelling | doaj.art-e62215ef8abc42659513d3485e9832fc2022-12-21T17:25:31ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862019-09-01219882892MicroRNA-130a modulates a radiosensitivity of rectal cancer by targeting SOX4Huyen Trang Ha Thi0Hye-Yeon Kim1Young-Mi Kim2Suntaek Hong3Laboratory of Cancer Cell Biology, Department of Biochemistry, Gachon University School of Medicine, Incheon 21999, Republic of KoreaLaboratory of Cancer Cell Biology, Department of Biochemistry, Gachon University School of Medicine, Incheon 21999, Republic of KoreaDepartment of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Republic of KoreaLaboratory of Cancer Cell Biology, Department of Biochemistry, Gachon University School of Medicine, Incheon 21999, Republic of Korea; Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Republic of Korea; Address all correspondence to: Suntaek Hong, Laboratory of Cancer Cell Biology, Department of Biochemistry, Gachon University School of Medicine, 155 Gaetbeol-ro Yeonsu-gu, Incheon 21999, Republic of Korea.Radioresistance poses a major challenge in the treatment of advanced rectal cancer. Therefore, understanding the detailed mechanisms of radioresistance may improve patient response to irradiation and the survival rate. To identify the novel targets that modulate the radiosensitivity of rectal cancer, we performed small RNA sequencing with human rectal cancer cell lines. Through bioinformatics analysis, we selected microRNA-310a (miR-130a) as a promising candidate to elucidate radioresistance. miR-130a was dramatically upregulated in radiosensitive rectal cancer cells and overexpression of miR-130a promotes rectal cancer cell radiosensitivity. Mechanically, miR-130a reversed the epithelial-mesenchymal transition phenotype of rectal cancer cells following inhibition of cell invasion upon irradiation. Moreover, miR-130a also inhibited the repair of irradiation-induced DNA damage followed by cell death. We identified that SOX4 was a direct target of miR-130a. Overexpression of SOX4 reversed the promotion activity of miR-130a on radiosensitivity. Together, our findings suggest that miR-130a functions as a radiosensitizer in rectal cancer and reveals a potential therapeutic target and preoperative prognostic marker for radiotherapy.http://www.sciencedirect.com/science/article/pii/S1476558619301678 |
spellingShingle | Huyen Trang Ha Thi Hye-Yeon Kim Young-Mi Kim Suntaek Hong MicroRNA-130a modulates a radiosensitivity of rectal cancer by targeting SOX4 Neoplasia: An International Journal for Oncology Research |
title | MicroRNA-130a modulates a radiosensitivity of rectal cancer by targeting SOX4 |
title_full | MicroRNA-130a modulates a radiosensitivity of rectal cancer by targeting SOX4 |
title_fullStr | MicroRNA-130a modulates a radiosensitivity of rectal cancer by targeting SOX4 |
title_full_unstemmed | MicroRNA-130a modulates a radiosensitivity of rectal cancer by targeting SOX4 |
title_short | MicroRNA-130a modulates a radiosensitivity of rectal cancer by targeting SOX4 |
title_sort | microrna 130a modulates a radiosensitivity of rectal cancer by targeting sox4 |
url | http://www.sciencedirect.com/science/article/pii/S1476558619301678 |
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