Evaluation of the lncRNA-miRNA-mRNA ceRNA network in lungs of miR-147 −/− mice

Background: Previous studies have documented important roles for microRNA-147 (miR-147) in inflammation, radiation-induced injury, cancer, and a range of other diseases. Murine lungs exhibit high levels of miRNA, mRNA, and lncRNA expression. However, very little research to date has focused on the l...

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Main Authors: Nan Zhang, Gui-Yuan Song, Qing-Hua Yu, Xin-Ming Fan, Wen-Shuo Zhang, Yong-Jian Hu, Tian-Zhu Chao, Yao-Yao Wu, Shu-Yan Duan, Fei Wang, Rui-Peng Du, Ping Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-03-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2024.1335374/full
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author Nan Zhang
Gui-Yuan Song
Gui-Yuan Song
Qing-Hua Yu
Qing-Hua Yu
Xin-Ming Fan
Wen-Shuo Zhang
Yong-Jian Hu
Tian-Zhu Chao
Yao-Yao Wu
Shu-Yan Duan
Fei Wang
Rui-Peng Du
Ping Xu
author_facet Nan Zhang
Gui-Yuan Song
Gui-Yuan Song
Qing-Hua Yu
Qing-Hua Yu
Xin-Ming Fan
Wen-Shuo Zhang
Yong-Jian Hu
Tian-Zhu Chao
Yao-Yao Wu
Shu-Yan Duan
Fei Wang
Rui-Peng Du
Ping Xu
author_sort Nan Zhang
collection DOAJ
description Background: Previous studies have documented important roles for microRNA-147 (miR-147) in inflammation, radiation-induced injury, cancer, and a range of other diseases. Murine lungs exhibit high levels of miRNA, mRNA, and lncRNA expression. However, very little research to date has focused on the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks associated with miR-147, and the regulation of lncRNAs and miRNAs in this setting remains poorly understood.Methods: After establishing a miR-147−/− model mouse, samples of lung tissue were harvested for RNA-sequencing, and differentially expressed lncRNAs, miRNAs, and mRNAs were identified. The miRNA targets of these lncRNAs and the identified miRNAs were first overlapped to facilitate the prediction of target mRNAs, with analyses then examining the overlap between these targets and mRNAs that were differentially expressed. Then, these target mRNAs were subjected to pathway enrichment analyses. These results were ultimately used to establish a miR-147-related ceRNA network.Results: Relative to wild-type mice, the lungs of miR-147−/− mice exhibited 91, 43, and 71 significantly upregulated lncRNAs, miRNAs, and mRNAs, respectively, together with 114, 31, and 156 that were significantly downregulated. The lncRNA-miRNA-mRNA network established based on these results led to the identification of Kcnh6 as a differentially expressed hub gene candidate and enabled the identification of a range of regulatory relationships. KEGG pathway enrichment showed that the mRNA targets of differentially expressed lncRNAs and miRNAs in the mice were associated with tumor-related signaling, endometrial cancer, bladder cancer, and ErbB signaling.Conclusion: These results suggest that the identified ceRNA network in miR-147−/− mice shapes tumor-associated signaling activity, with miR-147 potentially regulating various lncRNAs and miRNAs through Kcnh6, ultimately influencing tumorigenesis. Future studies of the lncRNA, miRNA, and mRNA regulatory targets shown to be associated with miR-147 in the present study may ultimately lead to the identification of novel clinically relevant targets through which miR-147 shapes the pathogenesis of cancer and other diseases.
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spelling doaj.art-ba0cc6788e5c4cd38ffd6286a20b15ef2024-03-06T14:19:17ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-03-011510.3389/fphar.2024.13353741335374Evaluation of the lncRNA-miRNA-mRNA ceRNA network in lungs of miR-147 −/− miceNan Zhang0Gui-Yuan Song1Gui-Yuan Song2Qing-Hua Yu3Qing-Hua Yu4Xin-Ming Fan5Wen-Shuo Zhang6Yong-Jian Hu7Tian-Zhu Chao8Yao-Yao Wu9Shu-Yan Duan10Fei Wang11Rui-Peng Du12Ping Xu13Laboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, ChinaLaboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, ChinaSchool of Pharmacy, Weifang Medical University, Weifang, Shandong, ChinaLaboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, ChinaSchool of Public Health, Weifang Medical University, Weifang, Shandong, ChinaDepartment of Radiotherapy, Zaozhuang Municipal Hospital, Zaozhuang, Shandong, ChinaDepartment of Radiotherapy, Zaozhuang Municipal Hospital, Zaozhuang, Shandong, ChinaHenan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan, ChinaLaboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, ChinaLaboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, ChinaLaboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, ChinaLaboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, ChinaLaboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, ChinaLaboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, ChinaBackground: Previous studies have documented important roles for microRNA-147 (miR-147) in inflammation, radiation-induced injury, cancer, and a range of other diseases. Murine lungs exhibit high levels of miRNA, mRNA, and lncRNA expression. However, very little research to date has focused on the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks associated with miR-147, and the regulation of lncRNAs and miRNAs in this setting remains poorly understood.Methods: After establishing a miR-147−/− model mouse, samples of lung tissue were harvested for RNA-sequencing, and differentially expressed lncRNAs, miRNAs, and mRNAs were identified. The miRNA targets of these lncRNAs and the identified miRNAs were first overlapped to facilitate the prediction of target mRNAs, with analyses then examining the overlap between these targets and mRNAs that were differentially expressed. Then, these target mRNAs were subjected to pathway enrichment analyses. These results were ultimately used to establish a miR-147-related ceRNA network.Results: Relative to wild-type mice, the lungs of miR-147−/− mice exhibited 91, 43, and 71 significantly upregulated lncRNAs, miRNAs, and mRNAs, respectively, together with 114, 31, and 156 that were significantly downregulated. The lncRNA-miRNA-mRNA network established based on these results led to the identification of Kcnh6 as a differentially expressed hub gene candidate and enabled the identification of a range of regulatory relationships. KEGG pathway enrichment showed that the mRNA targets of differentially expressed lncRNAs and miRNAs in the mice were associated with tumor-related signaling, endometrial cancer, bladder cancer, and ErbB signaling.Conclusion: These results suggest that the identified ceRNA network in miR-147−/− mice shapes tumor-associated signaling activity, with miR-147 potentially regulating various lncRNAs and miRNAs through Kcnh6, ultimately influencing tumorigenesis. Future studies of the lncRNA, miRNA, and mRNA regulatory targets shown to be associated with miR-147 in the present study may ultimately lead to the identification of novel clinically relevant targets through which miR-147 shapes the pathogenesis of cancer and other diseases.https://www.frontiersin.org/articles/10.3389/fphar.2024.1335374/fullmiRNA-147KCNH6ceRNAlncRNA-miRNA-mRNA networkcancer
spellingShingle Nan Zhang
Gui-Yuan Song
Gui-Yuan Song
Qing-Hua Yu
Qing-Hua Yu
Xin-Ming Fan
Wen-Shuo Zhang
Yong-Jian Hu
Tian-Zhu Chao
Yao-Yao Wu
Shu-Yan Duan
Fei Wang
Rui-Peng Du
Ping Xu
Evaluation of the lncRNA-miRNA-mRNA ceRNA network in lungs of miR-147 −/− mice
Frontiers in Pharmacology
miRNA-147
KCNH6
ceRNA
lncRNA-miRNA-mRNA network
cancer
title Evaluation of the lncRNA-miRNA-mRNA ceRNA network in lungs of miR-147 −/− mice
title_full Evaluation of the lncRNA-miRNA-mRNA ceRNA network in lungs of miR-147 −/− mice
title_fullStr Evaluation of the lncRNA-miRNA-mRNA ceRNA network in lungs of miR-147 −/− mice
title_full_unstemmed Evaluation of the lncRNA-miRNA-mRNA ceRNA network in lungs of miR-147 −/− mice
title_short Evaluation of the lncRNA-miRNA-mRNA ceRNA network in lungs of miR-147 −/− mice
title_sort evaluation of the lncrna mirna mrna cerna network in lungs of mir 147 mice
topic miRNA-147
KCNH6
ceRNA
lncRNA-miRNA-mRNA network
cancer
url https://www.frontiersin.org/articles/10.3389/fphar.2024.1335374/full
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