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miR-1301/TRIAP1 Axis Participates in Epirubicin-Mediated Anti-Proliferation and Pro-Apoptosis in Osteosarcoma

PURPOSE: Epirubicin is one of the most effective drugs against osteosarcoma. miR-1301 is involved in the occurrence and development of osteosarcoma. Whether miR-1301 is responsible for the chemosensitivity of osteosarcoma cells to epirubicin remains largely unknown. MATERIALS AND METHODS: U2OS and S...

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Autores principales: Yu, Lijun, Meng, Min, Bao, Yun, Zhang, Chao, Gao, Bei, Sa, Rina, Luo, Wenyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Yonsei University College of Medicine 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704023/
https://www.ncbi.nlm.nih.gov/pubmed/31433581
http://dx.doi.org/10.3349/ymj.2019.60.9.832
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author Yu, Lijun
Meng, Min
Bao, Yun
Zhang, Chao
Gao, Bei
Sa, Rina
Luo, Wenyuan
author_facet Yu, Lijun
Meng, Min
Bao, Yun
Zhang, Chao
Gao, Bei
Sa, Rina
Luo, Wenyuan
author_sort Yu, Lijun
collection PubMed
description PURPOSE: Epirubicin is one of the most effective drugs against osteosarcoma. miR-1301 is involved in the occurrence and development of osteosarcoma. Whether miR-1301 is responsible for the chemosensitivity of osteosarcoma cells to epirubicin remains largely unknown. MATERIALS AND METHODS: U2OS and SAOS-2 cells were treated with various concentrations of epirubicin. Flow cytometry was employed to evaluate cell apoptotic rate. Cell proliferation was measured by Cell Counting Kit-8 assay. Western blot and quantitative real-time polymerase chain reaction were utilized to detect the expressions of B-cell lymphoma-2 (Bcl-2), Bcl-2 assaciated X protein (Bax), cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerases (PARP1), TP53-regulated inhibitor of apoptosis 1 (TRIAP1), and microRNA-1301 (miR-1301). The relationship between miR-1301 and TRIAP1 was determined by luciferase reporter assay. RESULTS: Epirubicin inhibited proliferation in a dose-dependent manner, induced apoptosis, decreased the expression of Bcl-2, and increased the expressions of Bax, cleaved-caspase-3, and cleaved-PARP1 in osteosarcoma cells. miR-1301 was downregulated in U2OS and SAOS-2 cells. Importantly, epirubicin significantly increased the levels of miR-1301. Overexpression of miR-1301 suppressed proliferation and promoted apoptosis. Interestingly, those effects were enhanced by epirubicin. In contrast, miR-1301 depletion attenuated the epirubicin-mediated anti-osteosarcoma effect. miR-1301 negatively regulated the expression of TRIAP1 in U2OS and SAOS-2 cells. Furthermore, epirubicin inhibited the mRNA and protein levels of TRIAP1 by upregulating miR-1301 levels. Epirubicin suppressed cell proliferation by downregulating TRIAP1. CONCLUSION: miR-1301 was implicated in the chemosensitivity of osteosarcoma to epirubicin by modulating TRIAP1.
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spelling pubmed-67040232019-09-01 miR-1301/TRIAP1 Axis Participates in Epirubicin-Mediated Anti-Proliferation and Pro-Apoptosis in Osteosarcoma Yu, Lijun Meng, Min Bao, Yun Zhang, Chao Gao, Bei Sa, Rina Luo, Wenyuan Yonsei Med J Original Article PURPOSE: Epirubicin is one of the most effective drugs against osteosarcoma. miR-1301 is involved in the occurrence and development of osteosarcoma. Whether miR-1301 is responsible for the chemosensitivity of osteosarcoma cells to epirubicin remains largely unknown. MATERIALS AND METHODS: U2OS and SAOS-2 cells were treated with various concentrations of epirubicin. Flow cytometry was employed to evaluate cell apoptotic rate. Cell proliferation was measured by Cell Counting Kit-8 assay. Western blot and quantitative real-time polymerase chain reaction were utilized to detect the expressions of B-cell lymphoma-2 (Bcl-2), Bcl-2 assaciated X protein (Bax), cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerases (PARP1), TP53-regulated inhibitor of apoptosis 1 (TRIAP1), and microRNA-1301 (miR-1301). The relationship between miR-1301 and TRIAP1 was determined by luciferase reporter assay. RESULTS: Epirubicin inhibited proliferation in a dose-dependent manner, induced apoptosis, decreased the expression of Bcl-2, and increased the expressions of Bax, cleaved-caspase-3, and cleaved-PARP1 in osteosarcoma cells. miR-1301 was downregulated in U2OS and SAOS-2 cells. Importantly, epirubicin significantly increased the levels of miR-1301. Overexpression of miR-1301 suppressed proliferation and promoted apoptosis. Interestingly, those effects were enhanced by epirubicin. In contrast, miR-1301 depletion attenuated the epirubicin-mediated anti-osteosarcoma effect. miR-1301 negatively regulated the expression of TRIAP1 in U2OS and SAOS-2 cells. Furthermore, epirubicin inhibited the mRNA and protein levels of TRIAP1 by upregulating miR-1301 levels. Epirubicin suppressed cell proliferation by downregulating TRIAP1. CONCLUSION: miR-1301 was implicated in the chemosensitivity of osteosarcoma to epirubicin by modulating TRIAP1. Yonsei University College of Medicine 2019-09-01 2019-08-16 /pmc/articles/PMC6704023/ /pubmed/31433581 http://dx.doi.org/10.3349/ymj.2019.60.9.832 Text en © Copyright: Yonsei University College of Medicine 2019 https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Yu, Lijun
Meng, Min
Bao, Yun
Zhang, Chao
Gao, Bei
Sa, Rina
Luo, Wenyuan
miR-1301/TRIAP1 Axis Participates in Epirubicin-Mediated Anti-Proliferation and Pro-Apoptosis in Osteosarcoma
title miR-1301/TRIAP1 Axis Participates in Epirubicin-Mediated Anti-Proliferation and Pro-Apoptosis in Osteosarcoma
title_full miR-1301/TRIAP1 Axis Participates in Epirubicin-Mediated Anti-Proliferation and Pro-Apoptosis in Osteosarcoma
title_fullStr miR-1301/TRIAP1 Axis Participates in Epirubicin-Mediated Anti-Proliferation and Pro-Apoptosis in Osteosarcoma
title_full_unstemmed miR-1301/TRIAP1 Axis Participates in Epirubicin-Mediated Anti-Proliferation and Pro-Apoptosis in Osteosarcoma
title_short miR-1301/TRIAP1 Axis Participates in Epirubicin-Mediated Anti-Proliferation and Pro-Apoptosis in Osteosarcoma
title_sort mir-1301/triap1 axis participates in epirubicin-mediated anti-proliferation and pro-apoptosis in osteosarcoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704023/
https://www.ncbi.nlm.nih.gov/pubmed/31433581
http://dx.doi.org/10.3349/ymj.2019.60.9.832
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