LncRNA A2ml2 inhibits fatty liver hemorrhage syndrome progression and function as ceRNA to target LPL by sponging miR-143-5p

Fatty liver hemorrhage syndrome (FLHS) is the most common metabolic diseases in laying hens during the late-laying period, and it causes a significant economic burden on the poultry industry. The competing endogenous RNA plays crucial roles in the occurrence and development of fatty liver. Based on...

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Main Authors: Qingxing Xiao, Sibao Yang, Yuwei Yang, Hongyu Ni, Zongdi Li, Chengwen Wang, Wuyang Liu, Yuxin Han, Yumei Li, Yonghong Zhang
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Poultry Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S0032579125002421
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author Qingxing Xiao
Sibao Yang
Yuwei Yang
Hongyu Ni
Zongdi Li
Chengwen Wang
Wuyang Liu
Yuxin Han
Yumei Li
Yonghong Zhang
author_facet Qingxing Xiao
Sibao Yang
Yuwei Yang
Hongyu Ni
Zongdi Li
Chengwen Wang
Wuyang Liu
Yuxin Han
Yumei Li
Yonghong Zhang
author_sort Qingxing Xiao
collection DOAJ
description Fatty liver hemorrhage syndrome (FLHS) is the most common metabolic diseases in laying hens during the late-laying period, and it causes a significant economic burden on the poultry industry. The competing endogenous RNA plays crucial roles in the occurrence and development of fatty liver. Based on the previously constructed lncRNA-miRNA-mRNA networks, we selected the axis of ENSGALT00000079786-LPL-miR-143-5p for further study to elucidate its mechanistic role in development of fatty liver. In this study, we identified a novel highly conserved lncRNA (ENSGALT00000079786) in poultry, which we designated as lncRNA A2ml2 based on its chromosomal location. Fluorescent in situ hybridization (FISH) revealed that lncRNA A2ml2 was localized in both the nucleus and cytoplasm. Dual-luciferase reporter assay validated the targeted relationship between lncRNA A2ml2, miR-143-5p, and the LPL gene. To further analyze the lncRNA A2ml2 and miR-143-5p function, lncRNA A2ml2 overexpression vector was successfully constructed and transfected into Leghorn male hepatocellular (LMH) cells, which could remarkably inhibit cellular lipid deposition was detected by oil red staining (P < 0.01), the opposite occurred for miR-143-5p (P < 0.01). qPCR demonstrated an inverse correlation between miR-143-5p expression and lncRNA A2ml2 expression, and confirmed that miR-143-5p directly target lncRNA A2ml2. Similarly, we found an inverse correlation between expression of LPL and the expression of miR-143-5p. To further investigate the interactions among these three factors and their effects on cellular lipid metabolism, we assessed the expression levels of LPL by co-transfecting lncRNA A2ml2 with miR-143-5p mimic and miR-143-5p mimic binding site mutants. Co-transfection experiments showed that miR-143-5p diminished the promoting effect of lncRNA A2ml2 on LPL. Meanwhile, miR-143-5p has the capacity to mitigate the suppressive impact of lncRNA A2ml2 overexpression on lipid accumulation in LMH cells. The results revealed that lncRNA A2ml2 attenuated hepatic lipid accumulation through negatively regulating miR-143-5p and enhancing LPL expression in LMH cells. Our findings offer novel insights into ceRNA-mediated in FLHS and identify a novel lncRNA as a potential molecular biomarker.
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spelling doaj-art-ee3ea737ed0841fbaa8256dce715f0512025-08-20T03:49:41ZengElsevierPoultry Science0032-57912025-05-01104510500310.1016/j.psj.2025.105003LncRNA A2ml2 inhibits fatty liver hemorrhage syndrome progression and function as ceRNA to target LPL by sponging miR-143-5pQingxing Xiao0Sibao Yang1Yuwei Yang2Hongyu Ni3Zongdi Li4Chengwen Wang5Wuyang Liu6Yuxin Han7Yumei Li8Yonghong Zhang9College of Animal Science, Jilin University, Changchun, 130062, ChinaDepartment of Cardiovascular Medicine, China-Japan Union Hospital of Jilin University, No.126 Xiantai street of Changchun city, Jilin, 130031, ChinaCollege of Animal Science, Jilin University, Changchun, 130062, ChinaCollege of Animal Science, Jilin University, Changchun, 130062, ChinaCollege of Animal Science, Jilin University, Changchun, 130062, ChinaCollege of Animal Science, Jilin University, Changchun, 130062, ChinaCollege of Animal Science, Jilin University, Changchun, 130062, ChinaCollege of Animal Science, Jilin University, Changchun, 130062, ChinaCollege of Animal Science, Jilin University, Changchun, 130062, ChinaCollege of Animal Science, Jilin University, Changchun, 130062, China; Corresponding author: Yonghong Zhang, College of Animal Science, Jilin University, Changchun 130062, P. R. China; Tel: +86-0431-87836177, Fax: +86-0431-87836177Fatty liver hemorrhage syndrome (FLHS) is the most common metabolic diseases in laying hens during the late-laying period, and it causes a significant economic burden on the poultry industry. The competing endogenous RNA plays crucial roles in the occurrence and development of fatty liver. Based on the previously constructed lncRNA-miRNA-mRNA networks, we selected the axis of ENSGALT00000079786-LPL-miR-143-5p for further study to elucidate its mechanistic role in development of fatty liver. In this study, we identified a novel highly conserved lncRNA (ENSGALT00000079786) in poultry, which we designated as lncRNA A2ml2 based on its chromosomal location. Fluorescent in situ hybridization (FISH) revealed that lncRNA A2ml2 was localized in both the nucleus and cytoplasm. Dual-luciferase reporter assay validated the targeted relationship between lncRNA A2ml2, miR-143-5p, and the LPL gene. To further analyze the lncRNA A2ml2 and miR-143-5p function, lncRNA A2ml2 overexpression vector was successfully constructed and transfected into Leghorn male hepatocellular (LMH) cells, which could remarkably inhibit cellular lipid deposition was detected by oil red staining (P < 0.01), the opposite occurred for miR-143-5p (P < 0.01). qPCR demonstrated an inverse correlation between miR-143-5p expression and lncRNA A2ml2 expression, and confirmed that miR-143-5p directly target lncRNA A2ml2. Similarly, we found an inverse correlation between expression of LPL and the expression of miR-143-5p. To further investigate the interactions among these three factors and their effects on cellular lipid metabolism, we assessed the expression levels of LPL by co-transfecting lncRNA A2ml2 with miR-143-5p mimic and miR-143-5p mimic binding site mutants. Co-transfection experiments showed that miR-143-5p diminished the promoting effect of lncRNA A2ml2 on LPL. Meanwhile, miR-143-5p has the capacity to mitigate the suppressive impact of lncRNA A2ml2 overexpression on lipid accumulation in LMH cells. The results revealed that lncRNA A2ml2 attenuated hepatic lipid accumulation through negatively regulating miR-143-5p and enhancing LPL expression in LMH cells. Our findings offer novel insights into ceRNA-mediated in FLHS and identify a novel lncRNA as a potential molecular biomarker.http://www.sciencedirect.com/science/article/pii/S0032579125002421Fatty liver hemorrhage syndromelncRNA A2ml2miR-143-5p, LPLLipid metabolism
spellingShingle Qingxing Xiao
Sibao Yang
Yuwei Yang
Hongyu Ni
Zongdi Li
Chengwen Wang
Wuyang Liu
Yuxin Han
Yumei Li
Yonghong Zhang
LncRNA A2ml2 inhibits fatty liver hemorrhage syndrome progression and function as ceRNA to target LPL by sponging miR-143-5p
Poultry Science
Fatty liver hemorrhage syndrome
lncRNA A2ml2
miR-143-5p, LPL
Lipid metabolism
title LncRNA A2ml2 inhibits fatty liver hemorrhage syndrome progression and function as ceRNA to target LPL by sponging miR-143-5p
title_full LncRNA A2ml2 inhibits fatty liver hemorrhage syndrome progression and function as ceRNA to target LPL by sponging miR-143-5p
title_fullStr LncRNA A2ml2 inhibits fatty liver hemorrhage syndrome progression and function as ceRNA to target LPL by sponging miR-143-5p
title_full_unstemmed LncRNA A2ml2 inhibits fatty liver hemorrhage syndrome progression and function as ceRNA to target LPL by sponging miR-143-5p
title_short LncRNA A2ml2 inhibits fatty liver hemorrhage syndrome progression and function as ceRNA to target LPL by sponging miR-143-5p
title_sort lncrna a2ml2 inhibits fatty liver hemorrhage syndrome progression and function as cerna to target lpl by sponging mir 143 5p
topic Fatty liver hemorrhage syndrome
lncRNA A2ml2
miR-143-5p, LPL
Lipid metabolism
url http://www.sciencedirect.com/science/article/pii/S0032579125002421
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