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Exosomal Circ-XIAP Promotes Docetaxel Resistance in Prostate Cancer by Regulating miR-1182/TPD52 Axis
BACKGROUND: Exosomal circular RNAs (circRNAs) are involved in the pathogenesis of prostate cancer (PCa) and chemotherapy resistance. This research aimed to explore the function and molecular mechanism of circRNA X-linked inhibitor of apoptosis (circ-XIAP) in docetaxel (DTX) resistance of PCa. METHOD...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106459/ https://www.ncbi.nlm.nih.gov/pubmed/33976535 http://dx.doi.org/10.2147/DDDT.S300376 |
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author | Zhang, Hui Li, Minghui Zhang, Jing Shen, Yanbing Gui, Qi |
author_facet | Zhang, Hui Li, Minghui Zhang, Jing Shen, Yanbing Gui, Qi |
author_sort | Zhang, Hui |
collection | PubMed |
description | BACKGROUND: Exosomal circular RNAs (circRNAs) are involved in the pathogenesis of prostate cancer (PCa) and chemotherapy resistance. This research aimed to explore the function and molecular mechanism of circRNA X-linked inhibitor of apoptosis (circ-XIAP) in docetaxel (DTX) resistance of PCa. METHODS: The expression of circ-XIAP, microRNA-1182 (miR-1182), tumor protein D52 (TPD52) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were detected with transmission electron microscopy (TEM). Cluster of differentiation 63 (CD63), cluster of differentiation 9 (CD9) and TPD52 protein levels were detected by Western blot (WB). FIfty percent inhibitory concentration (IC50) of DTX and cell viability were determined using Cell Counting Kit-8 (CCK-8) assay. Colony formation assay was applied to assess colony-forming ability. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Transwell assay was used for measuring cell migration and invasion. Dual-reporter luciferase assay was performed to confirm the interaction between miR-1182 and circ-XIAP or TPD52. The role of circ-XIAP in vivo was confirmed via the mice xenograft model. RESULTS: Circ-XIAP and TPD52 were upregulated and miR-1182 was downregulated in DTX-resistant PCa tissue specimens and cell lines. Circ-XIAP was also overexpressed in exosomes from DTX-resistant cells and could be transmitted via exosomes. Circ-XIAP knockdown enhanced DTX sensitivity by suppressing DTX-resistant cell proliferation, migration and invasion and inducing cell cycle arrest and apoptosis. Circ-XIAP directly targeted miR-1182, and the effects of circ-XIAP knockdown were reversed by downregulating miR-1182 in DTX-resistant cells. TPD52 was the target of miR-1182, and its upregulation weakened the promotive effect of miR-1182 on DTX sensitivity. Importantly, circ-XIAP depletion inhibited tumor growth and increased DTX sensitivity in vivo. CONCLUSION: Exosomal circ-XIAP promoted DTX resistance of PCa by regulating miR-1182/TPD52 axis, providing a promising therapeutic target for PCa chemotherapy. |
format | Online Article Text |
id | pubmed-8106459 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-81064592021-05-10 Exosomal Circ-XIAP Promotes Docetaxel Resistance in Prostate Cancer by Regulating miR-1182/TPD52 Axis Zhang, Hui Li, Minghui Zhang, Jing Shen, Yanbing Gui, Qi Drug Des Devel Ther Original Research BACKGROUND: Exosomal circular RNAs (circRNAs) are involved in the pathogenesis of prostate cancer (PCa) and chemotherapy resistance. This research aimed to explore the function and molecular mechanism of circRNA X-linked inhibitor of apoptosis (circ-XIAP) in docetaxel (DTX) resistance of PCa. METHODS: The expression of circ-XIAP, microRNA-1182 (miR-1182), tumor protein D52 (TPD52) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were detected with transmission electron microscopy (TEM). Cluster of differentiation 63 (CD63), cluster of differentiation 9 (CD9) and TPD52 protein levels were detected by Western blot (WB). FIfty percent inhibitory concentration (IC50) of DTX and cell viability were determined using Cell Counting Kit-8 (CCK-8) assay. Colony formation assay was applied to assess colony-forming ability. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Transwell assay was used for measuring cell migration and invasion. Dual-reporter luciferase assay was performed to confirm the interaction between miR-1182 and circ-XIAP or TPD52. The role of circ-XIAP in vivo was confirmed via the mice xenograft model. RESULTS: Circ-XIAP and TPD52 were upregulated and miR-1182 was downregulated in DTX-resistant PCa tissue specimens and cell lines. Circ-XIAP was also overexpressed in exosomes from DTX-resistant cells and could be transmitted via exosomes. Circ-XIAP knockdown enhanced DTX sensitivity by suppressing DTX-resistant cell proliferation, migration and invasion and inducing cell cycle arrest and apoptosis. Circ-XIAP directly targeted miR-1182, and the effects of circ-XIAP knockdown were reversed by downregulating miR-1182 in DTX-resistant cells. TPD52 was the target of miR-1182, and its upregulation weakened the promotive effect of miR-1182 on DTX sensitivity. Importantly, circ-XIAP depletion inhibited tumor growth and increased DTX sensitivity in vivo. CONCLUSION: Exosomal circ-XIAP promoted DTX resistance of PCa by regulating miR-1182/TPD52 axis, providing a promising therapeutic target for PCa chemotherapy. Dove 2021-05-03 /pmc/articles/PMC8106459/ /pubmed/33976535 http://dx.doi.org/10.2147/DDDT.S300376 Text en © 2021 Zhang et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Zhang, Hui Li, Minghui Zhang, Jing Shen, Yanbing Gui, Qi Exosomal Circ-XIAP Promotes Docetaxel Resistance in Prostate Cancer by Regulating miR-1182/TPD52 Axis |
title | Exosomal Circ-XIAP Promotes Docetaxel Resistance in Prostate Cancer by Regulating miR-1182/TPD52 Axis |
title_full | Exosomal Circ-XIAP Promotes Docetaxel Resistance in Prostate Cancer by Regulating miR-1182/TPD52 Axis |
title_fullStr | Exosomal Circ-XIAP Promotes Docetaxel Resistance in Prostate Cancer by Regulating miR-1182/TPD52 Axis |
title_full_unstemmed | Exosomal Circ-XIAP Promotes Docetaxel Resistance in Prostate Cancer by Regulating miR-1182/TPD52 Axis |
title_short | Exosomal Circ-XIAP Promotes Docetaxel Resistance in Prostate Cancer by Regulating miR-1182/TPD52 Axis |
title_sort | exosomal circ-xiap promotes docetaxel resistance in prostate cancer by regulating mir-1182/tpd52 axis |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106459/ https://www.ncbi.nlm.nih.gov/pubmed/33976535 http://dx.doi.org/10.2147/DDDT.S300376 |
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