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Differential Expression of Super-Enhancer-Associated Long Non-coding RNAs in Uterine Leiomyomas

Super-enhancer-associated long non-coding RNAs (SE-lncRNAs) are a specific set of lncRNAs transcribed from super-enhancer (SE) genomic regions. Recent studies have revealed that SE-lncRNAs play essential roles in tumorigenesis through the regulation of oncogenes. The objective of this study was to e...

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Autores principales: Chuang, Tsai-Der, Quintanilla, Derek, Boos, Drake, Khorram, Omid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9537225/
https://www.ncbi.nlm.nih.gov/pubmed/35641855
http://dx.doi.org/10.1007/s43032-022-00981-4
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author Chuang, Tsai-Der
Quintanilla, Derek
Boos, Drake
Khorram, Omid
author_facet Chuang, Tsai-Der
Quintanilla, Derek
Boos, Drake
Khorram, Omid
author_sort Chuang, Tsai-Der
collection PubMed
description Super-enhancer-associated long non-coding RNAs (SE-lncRNAs) are a specific set of lncRNAs transcribed from super-enhancer (SE) genomic regions. Recent studies have revealed that SE-lncRNAs play essential roles in tumorigenesis through the regulation of oncogenes. The objective of this study was to elucidate the expression profile of SE-lncRNAs with concurrent assessment of associated mRNAs in leiomyomas and paired myometrium. Arraystar SE-lncRNAs arrays were used to systematically profile the differentially expressed SE-lncRNAs along with the corresponding SE-regulated protein coding genes in eight leiomyomas and paired myometrium. The analysis indicated 7680 SE-lncRNAs were expressed, of which 721 SE-lncRNAs were overexpressed, while 247 SE-lncRNAs were underexpressed by 1.5-fold or greater in leiomyoma. Thirteen novel SE-lncRNAs and their corresponding protein coding genes were selected, and their expression was confirmed in eighty-one paired leiomyoma tissues by quantitative real-time PCR. The thirteen pairs of SE-lncRNAs and their corresponding protein coding genes included RP11-353N14.2/CBX4, SOCS2-AS1/SOCS2, RP1-170O19.14/HOXA11, CASC15/PRL, EGFLAM-AS1/EGFLAM, RP11-225H22/NEURL1, RP5-1086K13.1/CD58, AC092839.3/SPTBN1, RP11-69I8.3/CTGF, TM4SF1-AS1/TM4SF1, RP11-373D23/FOSL2, RP11-399K21.11/COMTD1, and CTB-113P19.1/SPARC. Among these SE-lncRNAs, the expression of SOCS2-AS1/SOCS2, RP11-353N14.2/CBX4, RP1-170O19.14/HOXA11, and RP11-225H22/NEURL1 was significantly higher in African Americans as compared with Caucasians. The expression of RP11-353N14.2/CBX4, SOCS2-AS1/SOCS2, CASC15/PRL, and CTB-113P19.1/SPARC was significantly higher in tumors with MED12-mutation-positive as compared with MED12-mutation-negative tumors. Collectively, our results indicate that the differential expression of SE in leiomyomas is another mechanism contributing to dysregulation of protein coding genes in leiomyomas and that race and MED12 mutation can influence the expression of a select group of SE. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43032-022-00981-4.
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spelling pubmed-95372252022-10-08 Differential Expression of Super-Enhancer-Associated Long Non-coding RNAs in Uterine Leiomyomas Chuang, Tsai-Der Quintanilla, Derek Boos, Drake Khorram, Omid Reprod Sci Fibroid: Original Article Super-enhancer-associated long non-coding RNAs (SE-lncRNAs) are a specific set of lncRNAs transcribed from super-enhancer (SE) genomic regions. Recent studies have revealed that SE-lncRNAs play essential roles in tumorigenesis through the regulation of oncogenes. The objective of this study was to elucidate the expression profile of SE-lncRNAs with concurrent assessment of associated mRNAs in leiomyomas and paired myometrium. Arraystar SE-lncRNAs arrays were used to systematically profile the differentially expressed SE-lncRNAs along with the corresponding SE-regulated protein coding genes in eight leiomyomas and paired myometrium. The analysis indicated 7680 SE-lncRNAs were expressed, of which 721 SE-lncRNAs were overexpressed, while 247 SE-lncRNAs were underexpressed by 1.5-fold or greater in leiomyoma. Thirteen novel SE-lncRNAs and their corresponding protein coding genes were selected, and their expression was confirmed in eighty-one paired leiomyoma tissues by quantitative real-time PCR. The thirteen pairs of SE-lncRNAs and their corresponding protein coding genes included RP11-353N14.2/CBX4, SOCS2-AS1/SOCS2, RP1-170O19.14/HOXA11, CASC15/PRL, EGFLAM-AS1/EGFLAM, RP11-225H22/NEURL1, RP5-1086K13.1/CD58, AC092839.3/SPTBN1, RP11-69I8.3/CTGF, TM4SF1-AS1/TM4SF1, RP11-373D23/FOSL2, RP11-399K21.11/COMTD1, and CTB-113P19.1/SPARC. Among these SE-lncRNAs, the expression of SOCS2-AS1/SOCS2, RP11-353N14.2/CBX4, RP1-170O19.14/HOXA11, and RP11-225H22/NEURL1 was significantly higher in African Americans as compared with Caucasians. The expression of RP11-353N14.2/CBX4, SOCS2-AS1/SOCS2, CASC15/PRL, and CTB-113P19.1/SPARC was significantly higher in tumors with MED12-mutation-positive as compared with MED12-mutation-negative tumors. Collectively, our results indicate that the differential expression of SE in leiomyomas is another mechanism contributing to dysregulation of protein coding genes in leiomyomas and that race and MED12 mutation can influence the expression of a select group of SE. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43032-022-00981-4. Springer International Publishing 2022-05-31 /pmc/articles/PMC9537225/ /pubmed/35641855 http://dx.doi.org/10.1007/s43032-022-00981-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Fibroid: Original Article
Chuang, Tsai-Der
Quintanilla, Derek
Boos, Drake
Khorram, Omid
Differential Expression of Super-Enhancer-Associated Long Non-coding RNAs in Uterine Leiomyomas
title Differential Expression of Super-Enhancer-Associated Long Non-coding RNAs in Uterine Leiomyomas
title_full Differential Expression of Super-Enhancer-Associated Long Non-coding RNAs in Uterine Leiomyomas
title_fullStr Differential Expression of Super-Enhancer-Associated Long Non-coding RNAs in Uterine Leiomyomas
title_full_unstemmed Differential Expression of Super-Enhancer-Associated Long Non-coding RNAs in Uterine Leiomyomas
title_short Differential Expression of Super-Enhancer-Associated Long Non-coding RNAs in Uterine Leiomyomas
title_sort differential expression of super-enhancer-associated long non-coding rnas in uterine leiomyomas
topic Fibroid: Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9537225/
https://www.ncbi.nlm.nih.gov/pubmed/35641855
http://dx.doi.org/10.1007/s43032-022-00981-4
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