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A Subpathway and Target Gene Cluster-Based Approach Uncovers lncRNAs Associated with Human Primordial Follicle Activation

Long non-coding RNAs (lncRNAs) are emerging as a critical regulator in controlling the expression level of genes involved in cell differentiation and development. Primordial follicle activation (PFA) is the first step for follicle maturation, and excessive PFA results in premature ovarian insufficie...

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Detalles Bibliográficos
Autores principales: Zhang, Li, Zou, Jiyuan, Wang, Zhihao, Li, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10342156/
https://www.ncbi.nlm.nih.gov/pubmed/37445702
http://dx.doi.org/10.3390/ijms241310525
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author Zhang, Li
Zou, Jiyuan
Wang, Zhihao
Li, Lin
author_facet Zhang, Li
Zou, Jiyuan
Wang, Zhihao
Li, Lin
author_sort Zhang, Li
collection PubMed
description Long non-coding RNAs (lncRNAs) are emerging as a critical regulator in controlling the expression level of genes involved in cell differentiation and development. Primordial follicle activation (PFA) is the first step for follicle maturation, and excessive PFA results in premature ovarian insufficiency (POI). However, the correlation between lncRNA and cell differentiation was largely unknown, especially during PFA. In this study, we observed the expression level of lncRNA was more specific than protein-coding genes in both follicles and granulosa cells, suggesting lncRNA might play a crucial role in follicle development. Hence, a systematical framework was needed to infer the functions of lncRNAs during PFA. Additionally, an increasing number of studies indicate that the subpathway is more precise in reflecting biological processes than the entire pathway. Given the complex expression patterns of lncRNA target genes, target genes were further clustered based on their expression similarity and classification performance to reveal the activated/inhibited gene modules, which intuitively illustrated the diversity of lncRNA regulation. Moreover, the knockdown of SBF2-AS1 in the A549 cell line and ZFAS1 in the SK-Hep1 cell line further validated the function of SBF2-AS1 in regulating the Hippo signaling subpathway and ZFAS1 in the cell cycle subpathway. Overall, our findings demonstrated the importance of subpathway analysis in uncovering the functions of lncRNAs during PFA, and paved new avenues for future lncRNA-associated research.
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spelling pubmed-103421562023-07-14 A Subpathway and Target Gene Cluster-Based Approach Uncovers lncRNAs Associated with Human Primordial Follicle Activation Zhang, Li Zou, Jiyuan Wang, Zhihao Li, Lin Int J Mol Sci Article Long non-coding RNAs (lncRNAs) are emerging as a critical regulator in controlling the expression level of genes involved in cell differentiation and development. Primordial follicle activation (PFA) is the first step for follicle maturation, and excessive PFA results in premature ovarian insufficiency (POI). However, the correlation between lncRNA and cell differentiation was largely unknown, especially during PFA. In this study, we observed the expression level of lncRNA was more specific than protein-coding genes in both follicles and granulosa cells, suggesting lncRNA might play a crucial role in follicle development. Hence, a systematical framework was needed to infer the functions of lncRNAs during PFA. Additionally, an increasing number of studies indicate that the subpathway is more precise in reflecting biological processes than the entire pathway. Given the complex expression patterns of lncRNA target genes, target genes were further clustered based on their expression similarity and classification performance to reveal the activated/inhibited gene modules, which intuitively illustrated the diversity of lncRNA regulation. Moreover, the knockdown of SBF2-AS1 in the A549 cell line and ZFAS1 in the SK-Hep1 cell line further validated the function of SBF2-AS1 in regulating the Hippo signaling subpathway and ZFAS1 in the cell cycle subpathway. Overall, our findings demonstrated the importance of subpathway analysis in uncovering the functions of lncRNAs during PFA, and paved new avenues for future lncRNA-associated research. MDPI 2023-06-23 /pmc/articles/PMC10342156/ /pubmed/37445702 http://dx.doi.org/10.3390/ijms241310525 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Li
Zou, Jiyuan
Wang, Zhihao
Li, Lin
A Subpathway and Target Gene Cluster-Based Approach Uncovers lncRNAs Associated with Human Primordial Follicle Activation
title A Subpathway and Target Gene Cluster-Based Approach Uncovers lncRNAs Associated with Human Primordial Follicle Activation
title_full A Subpathway and Target Gene Cluster-Based Approach Uncovers lncRNAs Associated with Human Primordial Follicle Activation
title_fullStr A Subpathway and Target Gene Cluster-Based Approach Uncovers lncRNAs Associated with Human Primordial Follicle Activation
title_full_unstemmed A Subpathway and Target Gene Cluster-Based Approach Uncovers lncRNAs Associated with Human Primordial Follicle Activation
title_short A Subpathway and Target Gene Cluster-Based Approach Uncovers lncRNAs Associated with Human Primordial Follicle Activation
title_sort subpathway and target gene cluster-based approach uncovers lncrnas associated with human primordial follicle activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10342156/
https://www.ncbi.nlm.nih.gov/pubmed/37445702
http://dx.doi.org/10.3390/ijms241310525
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