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Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7

BACKGROUND: One of the main reasons for the failure of prostate cancer (PCa) treatment is the generation of chemoresistance. Circular RNA hsa_circ_0000735 (hsa_circ_0000735) is connected with the progression of cancer. Nevertheless, the role and regulatory mechanism of hsa_circ_0000735 in the resist...

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Autores principales: Gao, Yisheng, Liu, Jie, Huan, Jing, Che, Fengyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376840/
https://www.ncbi.nlm.nih.gov/pubmed/32714093
http://dx.doi.org/10.1186/s12935-020-01421-6
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author Gao, Yisheng
Liu, Jie
Huan, Jing
Che, Fengyuan
author_facet Gao, Yisheng
Liu, Jie
Huan, Jing
Che, Fengyuan
author_sort Gao, Yisheng
collection PubMed
description BACKGROUND: One of the main reasons for the failure of prostate cancer (PCa) treatment is the generation of chemoresistance. Circular RNA hsa_circ_0000735 (hsa_circ_0000735) is connected with the progression of cancer. Nevertheless, the role and regulatory mechanism of hsa_circ_0000735 in the resistance of PCa to docetaxel (DTX) are unclear. METHODS: Expression levels of hsa_circ_0000735 and miR-7-5p (miR-7) in tissue samples and cells were examined via quantitative real-time polymerase chain reaction (qRT-PCR). The DTX sensitivity, viability, colony formation, cell cycle progression, and apoptosis of DTX-resistant PCa cells were determined via Cell Counting Kit-8 (CCK-8), cell colony formation, or flow cytometry assays. The levels of multidrug resistance protein 1 (MDR1) protein, cyclinD1, and B cell lymphoma 2 (bcl-2) were detected by western blotting. The interaction between hsa_circ_0000735 and miR-7 was verified via dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. The role of hsa_circ_0000735 in vivo was validated through tumor formation experiments. RESULTS: Hsa_circ_0000735 was upregulated and miR-7 was downregulated in DTX-resistant PCa tissues and cells. High hsa_circ_0000735 expression had a shorter overall survival. Both hsa_circ_0000735 knockdown and miR-7 mimic boosted DTX sensitivity, constrained viability, colony formation, cell cycle progression, and fostered apoptosis of DTX-resistant PCa cells. Also, hsa_circ_0000735 silencing elevated DTX sensitivity and repressed tumor growth in PCa in vivo. Mechanistically, hsa_circ_0000735 served as a sponge for miR-7. MiR-7 inhibition overturned hsa_circ_0000735 silencing-mediated impacts on DTX sensitivity and the malignant behaviors of DTX-resistant PCa cells. CONCLUSION: Hsa_circ_0000735 downregulation boosted PCa sensitivity to DTX and reduced tumor growth via sponging miR-7, providing a promising prognostic biomarker and therapeutic target for PCa.
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spelling pubmed-73768402020-07-23 Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7 Gao, Yisheng Liu, Jie Huan, Jing Che, Fengyuan Cancer Cell Int Primary Research BACKGROUND: One of the main reasons for the failure of prostate cancer (PCa) treatment is the generation of chemoresistance. Circular RNA hsa_circ_0000735 (hsa_circ_0000735) is connected with the progression of cancer. Nevertheless, the role and regulatory mechanism of hsa_circ_0000735 in the resistance of PCa to docetaxel (DTX) are unclear. METHODS: Expression levels of hsa_circ_0000735 and miR-7-5p (miR-7) in tissue samples and cells were examined via quantitative real-time polymerase chain reaction (qRT-PCR). The DTX sensitivity, viability, colony formation, cell cycle progression, and apoptosis of DTX-resistant PCa cells were determined via Cell Counting Kit-8 (CCK-8), cell colony formation, or flow cytometry assays. The levels of multidrug resistance protein 1 (MDR1) protein, cyclinD1, and B cell lymphoma 2 (bcl-2) were detected by western blotting. The interaction between hsa_circ_0000735 and miR-7 was verified via dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. The role of hsa_circ_0000735 in vivo was validated through tumor formation experiments. RESULTS: Hsa_circ_0000735 was upregulated and miR-7 was downregulated in DTX-resistant PCa tissues and cells. High hsa_circ_0000735 expression had a shorter overall survival. Both hsa_circ_0000735 knockdown and miR-7 mimic boosted DTX sensitivity, constrained viability, colony formation, cell cycle progression, and fostered apoptosis of DTX-resistant PCa cells. Also, hsa_circ_0000735 silencing elevated DTX sensitivity and repressed tumor growth in PCa in vivo. Mechanistically, hsa_circ_0000735 served as a sponge for miR-7. MiR-7 inhibition overturned hsa_circ_0000735 silencing-mediated impacts on DTX sensitivity and the malignant behaviors of DTX-resistant PCa cells. CONCLUSION: Hsa_circ_0000735 downregulation boosted PCa sensitivity to DTX and reduced tumor growth via sponging miR-7, providing a promising prognostic biomarker and therapeutic target for PCa. BioMed Central 2020-07-22 /pmc/articles/PMC7376840/ /pubmed/32714093 http://dx.doi.org/10.1186/s12935-020-01421-6 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Gao, Yisheng
Liu, Jie
Huan, Jing
Che, Fengyuan
Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7
title Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7
title_full Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7
title_fullStr Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7
title_full_unstemmed Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7
title_short Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7
title_sort downregulation of circular rna hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging mir-7
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376840/
https://www.ncbi.nlm.nih.gov/pubmed/32714093
http://dx.doi.org/10.1186/s12935-020-01421-6
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