Construction and analysis of lncRNA-related ceRNA network in mouse model of methotrexate-induced neural tube defect under folate deficiency
Objective To construct a regulatory network of long noncoding RNA (lncRNA)-related competing endogenous RNAs (ceRNA) in low folate combined with methotrexate (MTX) induced neural tube defects (NTDs) mouse model, and to explore the potential lncRNAs regulation in low folate-induced NTDs. Methods Fort...
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Editorial Office of Journal of Army Medical University
2023-01-01
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| Series: | 陆军军医大学学报 |
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| Online Access: | http://202.202.232.58/Upload/rhtml/202203181.htm |
| _version_ | 1797955510041837568 |
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| author | ZENG Yubing LIU Fan LIU Fan PEI Pe WANG Shan |
| author_facet | ZENG Yubing LIU Fan LIU Fan PEI Pe WANG Shan |
| author_sort | ZENG Yubing |
| collection | DOAJ |
| description | Objective To construct a regulatory network of long noncoding RNA (lncRNA)-related competing endogenous RNAs (ceRNA) in low folate combined with methotrexate (MTX) induced neural tube defects (NTDs) mouse model, and to explore the potential lncRNAs regulation in low folate-induced NTDs. Methods Forty SPF-grade 7~8-week-old healthy female C57BL/6J mice (body weight 18~22 g) and 20 healthy male C57BL/6J mice (20~22 g) were selected to this experiment. After a folate deficiency induced fetal mouse NTD model was successfully established, the embryonic brain tissues were extracted for total RNA and RNA high-throughput sequencing (RNA-seq) was performed. The results of RNA-seq were used to carry out co-expression network construction, GO function enrichment of mRNA in co-expression network and KEGG pathway enrichment analysis, construction of lncRNA-related ceRNA regulation network and other bioinformatics analysis. And the relative expression of lncRNA Xist, Sema4f and Padi2 in the fetal mouse and cell samples was verified by qPCR. Results A total of 47 differential lncRNAs (Log2FC >0.585 or Log2FC < -0.585, FDR < 0.05) were detected by RNA-seq, of which 38 were up-regulated and 9 were down-regulated. The co-expression network between lncRNA and mRNA was constructed. The results of KEGG/GO analysis on mRNAs in the co-expression network indicated that tube development (P < 0.001), collagen metabolic process (P=0.002), system development (P=0.002) and other significant enrichments were highly relevant to NTDs. Besides, KEGG pathway analysis displayed that the PI3K-Akt pathway was closely related to NTDs; lncRNA Xist, LOC102633899, 1700086L19Rik and other targeting differential genes Sema4f, Padi2, Lin28a were found in the lncRNA-related ceRNA network. qPCR confirmed that the above results in the fetal mice and cell samples under folic acid deficiency, with consistent corresponding sequences, and obviously down-regulated (P < 0.05). Conclusion In folic acid deficiency-induced mouse NTD model, lncRNA Xist, and its targeting genes Sema4f and Padi2 are obviously down-regulated.
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| first_indexed | 2024-04-10T23:35:21Z |
| format | Article |
| id | doaj.art-b5203fe3d8ae4e9a9d50732a8a919171 |
| institution | Directory Open Access Journal |
| issn | 2097-0927 |
| language | zho |
| last_indexed | 2024-04-10T23:35:21Z |
| publishDate | 2023-01-01 |
| publisher | Editorial Office of Journal of Army Medical University |
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| series | 陆军军医大学学报 |
| spelling | doaj.art-b5203fe3d8ae4e9a9d50732a8a9191712023-01-12T00:04:46ZzhoEditorial Office of Journal of Army Medical University陆军军医大学学报2097-09272023-01-014511910.16016/j.2097-0927.202203181Construction and analysis of lncRNA-related ceRNA network in mouse model of methotrexate-induced neural tube defect under folate deficiencyZENG Yubing0LIU Fan1LIU Fan2PEI Pe3WANG Shan4Beijing Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, 100020Beijing Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, 100020Graduate School of Peking Union Medical College, Beijing, 100020, ChinaBeijing Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, 100020Beijing Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, 100020Objective To construct a regulatory network of long noncoding RNA (lncRNA)-related competing endogenous RNAs (ceRNA) in low folate combined with methotrexate (MTX) induced neural tube defects (NTDs) mouse model, and to explore the potential lncRNAs regulation in low folate-induced NTDs. Methods Forty SPF-grade 7~8-week-old healthy female C57BL/6J mice (body weight 18~22 g) and 20 healthy male C57BL/6J mice (20~22 g) were selected to this experiment. After a folate deficiency induced fetal mouse NTD model was successfully established, the embryonic brain tissues were extracted for total RNA and RNA high-throughput sequencing (RNA-seq) was performed. The results of RNA-seq were used to carry out co-expression network construction, GO function enrichment of mRNA in co-expression network and KEGG pathway enrichment analysis, construction of lncRNA-related ceRNA regulation network and other bioinformatics analysis. And the relative expression of lncRNA Xist, Sema4f and Padi2 in the fetal mouse and cell samples was verified by qPCR. Results A total of 47 differential lncRNAs (Log2FC >0.585 or Log2FC < -0.585, FDR < 0.05) were detected by RNA-seq, of which 38 were up-regulated and 9 were down-regulated. The co-expression network between lncRNA and mRNA was constructed. The results of KEGG/GO analysis on mRNAs in the co-expression network indicated that tube development (P < 0.001), collagen metabolic process (P=0.002), system development (P=0.002) and other significant enrichments were highly relevant to NTDs. Besides, KEGG pathway analysis displayed that the PI3K-Akt pathway was closely related to NTDs; lncRNA Xist, LOC102633899, 1700086L19Rik and other targeting differential genes Sema4f, Padi2, Lin28a were found in the lncRNA-related ceRNA network. qPCR confirmed that the above results in the fetal mice and cell samples under folic acid deficiency, with consistent corresponding sequences, and obviously down-regulated (P < 0.05). Conclusion In folic acid deficiency-induced mouse NTD model, lncRNA Xist, and its targeting genes Sema4f and Padi2 are obviously down-regulated. http://202.202.232.58/Upload/rhtml/202203181.htmneural tube defectsepigeneticslong noncoding rnacompeting endogenous rna |
| spellingShingle | ZENG Yubing LIU Fan LIU Fan PEI Pe WANG Shan Construction and analysis of lncRNA-related ceRNA network in mouse model of methotrexate-induced neural tube defect under folate deficiency 陆军军医大学学报 neural tube defects epigenetics long noncoding rna competing endogenous rna |
| title | Construction and analysis of lncRNA-related ceRNA network in mouse model of methotrexate-induced neural tube defect under folate deficiency |
| title_full | Construction and analysis of lncRNA-related ceRNA network in mouse model of methotrexate-induced neural tube defect under folate deficiency |
| title_fullStr | Construction and analysis of lncRNA-related ceRNA network in mouse model of methotrexate-induced neural tube defect under folate deficiency |
| title_full_unstemmed | Construction and analysis of lncRNA-related ceRNA network in mouse model of methotrexate-induced neural tube defect under folate deficiency |
| title_short | Construction and analysis of lncRNA-related ceRNA network in mouse model of methotrexate-induced neural tube defect under folate deficiency |
| title_sort | construction and analysis of lncrna related cerna network in mouse model of methotrexate induced neural tube defect under folate deficiency |
| topic | neural tube defects epigenetics long noncoding rna competing endogenous rna |
| url | http://202.202.232.58/Upload/rhtml/202203181.htm |
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