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LncRNA PCAT6 regulates the progression of pituitary adenomas by regulating the miR-139-3p/BRD4 axis

BACKGROUND: Dysregulated lncRNA PCAT6 was discovered in many cancers excluding pituitary adenomas (PA). Therefore, we explored the role of PCAT6 in PA in this research. METHODS: Abnormally expressed miRNAs were analyzed by bioinformatics and RT-qPCR. The target and regulator of miR-139-3p were deter...

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Autores principales: Zhao, Peng, Cheng, Jianhua, Li, Bin, Nie, Ding, Wang, Hongyun, Li, Chuzhong, Gui, Songbai, Zhang, Yazhuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789787/
https://www.ncbi.nlm.nih.gov/pubmed/33407504
http://dx.doi.org/10.1186/s12935-020-01698-7
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author Zhao, Peng
Cheng, Jianhua
Li, Bin
Nie, Ding
Wang, Hongyun
Li, Chuzhong
Gui, Songbai
Zhang, Yazhuo
author_facet Zhao, Peng
Cheng, Jianhua
Li, Bin
Nie, Ding
Wang, Hongyun
Li, Chuzhong
Gui, Songbai
Zhang, Yazhuo
author_sort Zhao, Peng
collection PubMed
description BACKGROUND: Dysregulated lncRNA PCAT6 was discovered in many cancers excluding pituitary adenomas (PA). Therefore, we explored the role of PCAT6 in PA in this research. METHODS: Abnormally expressed miRNAs were analyzed by bioinformatics and RT-qPCR. The target and regulator of miR-139-3p were determined by bioinformatics, dual-luciferase reporter assay, or RIP. The correlation among PCAT6, miR-139-3p, and BRD4 was further analyzed. The viability, apoptosis, cell cycle distribution of PA cells, as well as their ability to invade, migrate, and proliferate, were tested after transfection through CCK-8, flow cytometry, transwell, wound healing, and colony formation assays. After construction of transplanted-tumor model in nude mice, cell apoptosis in the tumor was detected by TUNEL. The expressions of PCAT6, BRD4, miR-139-3p, and apoptosis-related factors in PA tissues, cells, or tumor tissues were detected by RT-qPCR, Western blot, or IHC. RESULTS: PCAT6 and BRD4 were high-expressed but miR-139-3p was low-expressed in PA. Both the 3′-untranslated regions of PCAT6 and BRD4 mRNAs were demonstrated to contain a potential binding site for miR-139-3p. PCAT6 was positively correlated to BRD4, and miR-139-3p was negatively correlated to PCAT6 and BRD4. MiR-139-3p mimic, shPCAT6 and siBRD4 inhibited the viability, migration, invasion, and proliferation of PA cells while inducing apoptosis. MiR-139-3p mimic and shPCAT6 inhibited the cell cycle progression of PA cells, decreased the weight and volume of the xenotransplanted tumor, and reduced the levels of Bcl-2 and BRD4 while enhancing the levels of Bax, miR-139-3p, and Cleaved caspase-3. MiR-139-3p inhibitor caused the opposite effect of miR-139-3p mimic and further reversed the effect of shPCAT6 on on PA cells. CONCLUSION: PCAT6 regulated the progression of PA via modulating the miR-139-3p/BRD4 axis, which might provide a novel biomarker for the prevention, diagnosis, and treatment of PA.
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spelling pubmed-77897872021-01-11 LncRNA PCAT6 regulates the progression of pituitary adenomas by regulating the miR-139-3p/BRD4 axis Zhao, Peng Cheng, Jianhua Li, Bin Nie, Ding Wang, Hongyun Li, Chuzhong Gui, Songbai Zhang, Yazhuo Cancer Cell Int Primary Research BACKGROUND: Dysregulated lncRNA PCAT6 was discovered in many cancers excluding pituitary adenomas (PA). Therefore, we explored the role of PCAT6 in PA in this research. METHODS: Abnormally expressed miRNAs were analyzed by bioinformatics and RT-qPCR. The target and regulator of miR-139-3p were determined by bioinformatics, dual-luciferase reporter assay, or RIP. The correlation among PCAT6, miR-139-3p, and BRD4 was further analyzed. The viability, apoptosis, cell cycle distribution of PA cells, as well as their ability to invade, migrate, and proliferate, were tested after transfection through CCK-8, flow cytometry, transwell, wound healing, and colony formation assays. After construction of transplanted-tumor model in nude mice, cell apoptosis in the tumor was detected by TUNEL. The expressions of PCAT6, BRD4, miR-139-3p, and apoptosis-related factors in PA tissues, cells, or tumor tissues were detected by RT-qPCR, Western blot, or IHC. RESULTS: PCAT6 and BRD4 were high-expressed but miR-139-3p was low-expressed in PA. Both the 3′-untranslated regions of PCAT6 and BRD4 mRNAs were demonstrated to contain a potential binding site for miR-139-3p. PCAT6 was positively correlated to BRD4, and miR-139-3p was negatively correlated to PCAT6 and BRD4. MiR-139-3p mimic, shPCAT6 and siBRD4 inhibited the viability, migration, invasion, and proliferation of PA cells while inducing apoptosis. MiR-139-3p mimic and shPCAT6 inhibited the cell cycle progression of PA cells, decreased the weight and volume of the xenotransplanted tumor, and reduced the levels of Bcl-2 and BRD4 while enhancing the levels of Bax, miR-139-3p, and Cleaved caspase-3. MiR-139-3p inhibitor caused the opposite effect of miR-139-3p mimic and further reversed the effect of shPCAT6 on on PA cells. CONCLUSION: PCAT6 regulated the progression of PA via modulating the miR-139-3p/BRD4 axis, which might provide a novel biomarker for the prevention, diagnosis, and treatment of PA. BioMed Central 2021-01-06 /pmc/articles/PMC7789787/ /pubmed/33407504 http://dx.doi.org/10.1186/s12935-020-01698-7 Text en © The Author(s) 2021 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
Zhao, Peng
Cheng, Jianhua
Li, Bin
Nie, Ding
Wang, Hongyun
Li, Chuzhong
Gui, Songbai
Zhang, Yazhuo
LncRNA PCAT6 regulates the progression of pituitary adenomas by regulating the miR-139-3p/BRD4 axis
title LncRNA PCAT6 regulates the progression of pituitary adenomas by regulating the miR-139-3p/BRD4 axis
title_full LncRNA PCAT6 regulates the progression of pituitary adenomas by regulating the miR-139-3p/BRD4 axis
title_fullStr LncRNA PCAT6 regulates the progression of pituitary adenomas by regulating the miR-139-3p/BRD4 axis
title_full_unstemmed LncRNA PCAT6 regulates the progression of pituitary adenomas by regulating the miR-139-3p/BRD4 axis
title_short LncRNA PCAT6 regulates the progression of pituitary adenomas by regulating the miR-139-3p/BRD4 axis
title_sort lncrna pcat6 regulates the progression of pituitary adenomas by regulating the mir-139-3p/brd4 axis
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789787/
https://www.ncbi.nlm.nih.gov/pubmed/33407504
http://dx.doi.org/10.1186/s12935-020-01698-7
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