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Pathological stage-associated non-coding RNA long intergenic non-protein coding RNA 1234 (LINC01234) participation in cell cycle regulation in adrenocortical carcinoma through bromodomain-containing protein 4 (BRD4) expression mediation via sponging microRNA (miR)-140-3p
Many researches indicated that long non-coding RNAs (lncRNAs) were involved in the malignant progression of tumors, including Adrenocortical Carcinoma (ACC). However, as for most lncRNAs, their biological behaviors and molecular mechanism remain unclear in ACC. In the present research, weighted gene...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275903/ https://www.ncbi.nlm.nih.gov/pubmed/35765893 http://dx.doi.org/10.1080/21655979.2022.2081464 |
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author | Zhu, Dan-Dan Yu, Xin-Bo Jiang, Wen Zhu, Yu |
author_facet | Zhu, Dan-Dan Yu, Xin-Bo Jiang, Wen Zhu, Yu |
author_sort | Zhu, Dan-Dan |
collection | PubMed |
description | Many researches indicated that long non-coding RNAs (lncRNAs) were involved in the malignant progression of tumors, including Adrenocortical Carcinoma (ACC). However, as for most lncRNAs, their biological behaviors and molecular mechanism remain unclear in ACC. In the present research, weighted gene co-expression network analysis (WGCNA) was used to identify pathologically relevant gene, including lncRNAs. By comparing their expressions in GSE61359 tumors and normal controls, long intergenic non-protein coding RNA 1234 (LINC01234) was selected to investigate the clinical significance, biological function, and mechanism in ACC. Data mining revealed that LINC01234 expression was significantly up-regulated in ACC patients, and a shorter survival time presents in patients with higher LINC01234 expression compared to that in patients with lower LINC01234 expression. Further, LINC01234 silencing resulted in cells growth arrest in vitro and in vivo. Mechanism studies suggested that LINC01234 silencing induced cell cycle arrest, and bromodomain-containing protein 4 (BRD4) overexpression could restore this phenomenon. Further research showed that LINC01234 could mediate BRD4 expression through competitively sequestering microRNA (miR)-140-3p, as evidenced by the positive correlation of LINC01234 with BRD4 and inverse correlation with miR-140-3p expression. Luciferase activity assay also verified the targeting relationship between LINC01234, BRD4 and miR-140-3p. And up-regulated LINC01234 in ACC cells significantly reversed the degradation of BRD4 by miR-140-3p. Collectively, we deduce that LINC01234 functions as a ceRNA to regulate BRD4 expression by sponging miR-140-3p in ACC progress. Our findings have the potential to provide a new target for the diagnosis and treatment of ACC. |
format | Online Article Text |
id | pubmed-9275903 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-92759032022-07-13 Pathological stage-associated non-coding RNA long intergenic non-protein coding RNA 1234 (LINC01234) participation in cell cycle regulation in adrenocortical carcinoma through bromodomain-containing protein 4 (BRD4) expression mediation via sponging microRNA (miR)-140-3p Zhu, Dan-Dan Yu, Xin-Bo Jiang, Wen Zhu, Yu Bioengineered Research Paper Many researches indicated that long non-coding RNAs (lncRNAs) were involved in the malignant progression of tumors, including Adrenocortical Carcinoma (ACC). However, as for most lncRNAs, their biological behaviors and molecular mechanism remain unclear in ACC. In the present research, weighted gene co-expression network analysis (WGCNA) was used to identify pathologically relevant gene, including lncRNAs. By comparing their expressions in GSE61359 tumors and normal controls, long intergenic non-protein coding RNA 1234 (LINC01234) was selected to investigate the clinical significance, biological function, and mechanism in ACC. Data mining revealed that LINC01234 expression was significantly up-regulated in ACC patients, and a shorter survival time presents in patients with higher LINC01234 expression compared to that in patients with lower LINC01234 expression. Further, LINC01234 silencing resulted in cells growth arrest in vitro and in vivo. Mechanism studies suggested that LINC01234 silencing induced cell cycle arrest, and bromodomain-containing protein 4 (BRD4) overexpression could restore this phenomenon. Further research showed that LINC01234 could mediate BRD4 expression through competitively sequestering microRNA (miR)-140-3p, as evidenced by the positive correlation of LINC01234 with BRD4 and inverse correlation with miR-140-3p expression. Luciferase activity assay also verified the targeting relationship between LINC01234, BRD4 and miR-140-3p. And up-regulated LINC01234 in ACC cells significantly reversed the degradation of BRD4 by miR-140-3p. Collectively, we deduce that LINC01234 functions as a ceRNA to regulate BRD4 expression by sponging miR-140-3p in ACC progress. Our findings have the potential to provide a new target for the diagnosis and treatment of ACC. Taylor & Francis 2022-06-29 /pmc/articles/PMC9275903/ /pubmed/35765893 http://dx.doi.org/10.1080/21655979.2022.2081464 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Zhu, Dan-Dan Yu, Xin-Bo Jiang, Wen Zhu, Yu Pathological stage-associated non-coding RNA long intergenic non-protein coding RNA 1234 (LINC01234) participation in cell cycle regulation in adrenocortical carcinoma through bromodomain-containing protein 4 (BRD4) expression mediation via sponging microRNA (miR)-140-3p |
title | Pathological stage-associated non-coding RNA long intergenic non-protein coding RNA 1234 (LINC01234) participation in cell cycle regulation in adrenocortical carcinoma through bromodomain-containing protein 4 (BRD4) expression mediation via sponging microRNA (miR)-140-3p |
title_full | Pathological stage-associated non-coding RNA long intergenic non-protein coding RNA 1234 (LINC01234) participation in cell cycle regulation in adrenocortical carcinoma through bromodomain-containing protein 4 (BRD4) expression mediation via sponging microRNA (miR)-140-3p |
title_fullStr | Pathological stage-associated non-coding RNA long intergenic non-protein coding RNA 1234 (LINC01234) participation in cell cycle regulation in adrenocortical carcinoma through bromodomain-containing protein 4 (BRD4) expression mediation via sponging microRNA (miR)-140-3p |
title_full_unstemmed | Pathological stage-associated non-coding RNA long intergenic non-protein coding RNA 1234 (LINC01234) participation in cell cycle regulation in adrenocortical carcinoma through bromodomain-containing protein 4 (BRD4) expression mediation via sponging microRNA (miR)-140-3p |
title_short | Pathological stage-associated non-coding RNA long intergenic non-protein coding RNA 1234 (LINC01234) participation in cell cycle regulation in adrenocortical carcinoma through bromodomain-containing protein 4 (BRD4) expression mediation via sponging microRNA (miR)-140-3p |
title_sort | pathological stage-associated non-coding rna long intergenic non-protein coding rna 1234 (linc01234) participation in cell cycle regulation in adrenocortical carcinoma through bromodomain-containing protein 4 (brd4) expression mediation via sponging microrna (mir)-140-3p |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275903/ https://www.ncbi.nlm.nih.gov/pubmed/35765893 http://dx.doi.org/10.1080/21655979.2022.2081464 |
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