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LncRNA pathway involved in premature preterm rupture of membrane (PPROM): an epigenomic approach to study the pathogenesis of reproductive disorders.

Luo X, Shi Q, Gu Y, Pan J, Hua M, Liu M, Dong Z, Zhang M, Wang L, Gu Y, Zhong J, Zhao X, Jenkins EC, Brown WT, Zhong N - PLoS ONE (2013)

Bottom Line: Our results showed that 22 pathways were characterized as up-regulated 7 down-regulated in A vs.C, 18 up-regulated and 15 down-regulated in A vs.D, and 33 up-regulated and 7 down-regulated in A vs.

View Article: PubMed Central - PubMed

Affiliation: Center of Translational Medicine for Maternal and Children's Health, Lianyungang Maternal and Children's Hospital, Lianyungang, Jiangsu, China.

ABSTRACT
Preterm birth (PTB) is a live birth delivered before 37 weeks of gestation (GW). About one-third of PTBs result from the preterm premature rupture of membranes (PPROM). Up to the present, the pathogenic mechanisms underlying PPROM are not clearly understood. Here, we investigated the differential expression of long chain non-coding RNAs (lncRNAs) in placentas of PTBs with PPROM, and their possible involvement in the pathogenic pathways leading to PPROM. A total number of 1954, 776, and 1050 lncRNAs were identified with a microarray from placentas of PPROM (group A), which were compared to full-term birth (FTB) (group B), PTB (group C), and premature rupture of membrane (PROM) (group D) at full-term, respectively. Instead of investigating the individual pathogenic role of each lncRNA involved in the molecular mechanism underlying PPROM, we have focused on investigating the metabolic pathways and their functions to explore what is the likely association and how they are possibly involved in the development of PPROM. Six groups, including up-regulation and down-regulation in the comparisons of A vs. B, A vs. C, and A vs. D, of pathways were analyzed. Our results showed that 22 pathways were characterized as up-regulated 7 down-regulated in A vs. C, 18 up-regulated and 15 down-regulated in A vs. D, and 33 up-regulated and 7 down-regulated in A vs. B. Functional analysis showed pathways of infection and inflammatory response, ECM-receptor interactions, apoptosis, actin cytoskeleton, and smooth muscle contraction are the major pathogenic mechanisms involved in the development of PPROM. Characterization of these pathways through identification of lncRNAs opened new avenues for further investigating the epigenomic mechanisms of lncRNAs in PPROM as well as PTB.

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Related in: MedlinePlus

GO molecular functional annotations.Functional relationship presented with GO “trees” for the top 10 (p<0.005) GO annotations (Table 3) is shown for both up- and down-regulated A vs. B, A vs. C, and A vs. D. The red color labels indicate the top 10 GOs. The yellow colors show GOs with lower p value, which were not presented in Table 3 but could be identified from the differentially expressed lncRNAs in PPROM, FT, PRTB, and PROM.
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pone-0079897-g004: GO molecular functional annotations.Functional relationship presented with GO “trees” for the top 10 (p<0.005) GO annotations (Table 3) is shown for both up- and down-regulated A vs. B, A vs. C, and A vs. D. The red color labels indicate the top 10 GOs. The yellow colors show GOs with lower p value, which were not presented in Table 3 but could be identified from the differentially expressed lncRNAs in PPROM, FT, PRTB, and PROM.

Mentions: The Gene Ontology (GO) website (http://www.geneontology.org) provides a controlled vocabulary to describe gene and gene product attributes in any organism. The ontology covers three domains: Biological Process, Cellular Component and Molecular Function. Fisher's exact test was used to determine if there is more overlap between the list of PPROM vs. controls and that of GO annotation than expected by chance. The p-value denotes the significance of GO terms enrichment in the A vs. C, A vs. D, and A vs. B genes. The lower the p-value (p-value<0.05 was applied), the more significant is the GO Term. Top 10 gene ontology (GO) molecular function annotations for lncRNAs (Table 4), based on their p values, showed their relative relationship with each other (Figure 4). Each color labeled box or circle represents a GO functional pathway. Red color labels indicate that these GO pathways are associated with PPROM and yellow labels were not detected from PPROM in this study. The order of the number represents the p value for how significant it is associated with PPROM.


LncRNA pathway involved in premature preterm rupture of membrane (PPROM): an epigenomic approach to study the pathogenesis of reproductive disorders.

Luo X, Shi Q, Gu Y, Pan J, Hua M, Liu M, Dong Z, Zhang M, Wang L, Gu Y, Zhong J, Zhao X, Jenkins EC, Brown WT, Zhong N - PLoS ONE (2013)

GO molecular functional annotations.Functional relationship presented with GO “trees” for the top 10 (p<0.005) GO annotations (Table 3) is shown for both up- and down-regulated A vs. B, A vs. C, and A vs. D. The red color labels indicate the top 10 GOs. The yellow colors show GOs with lower p value, which were not presented in Table 3 but could be identified from the differentially expressed lncRNAs in PPROM, FT, PRTB, and PROM.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842261&req=5

pone-0079897-g004: GO molecular functional annotations.Functional relationship presented with GO “trees” for the top 10 (p<0.005) GO annotations (Table 3) is shown for both up- and down-regulated A vs. B, A vs. C, and A vs. D. The red color labels indicate the top 10 GOs. The yellow colors show GOs with lower p value, which were not presented in Table 3 but could be identified from the differentially expressed lncRNAs in PPROM, FT, PRTB, and PROM.
Mentions: The Gene Ontology (GO) website (http://www.geneontology.org) provides a controlled vocabulary to describe gene and gene product attributes in any organism. The ontology covers three domains: Biological Process, Cellular Component and Molecular Function. Fisher's exact test was used to determine if there is more overlap between the list of PPROM vs. controls and that of GO annotation than expected by chance. The p-value denotes the significance of GO terms enrichment in the A vs. C, A vs. D, and A vs. B genes. The lower the p-value (p-value<0.05 was applied), the more significant is the GO Term. Top 10 gene ontology (GO) molecular function annotations for lncRNAs (Table 4), based on their p values, showed their relative relationship with each other (Figure 4). Each color labeled box or circle represents a GO functional pathway. Red color labels indicate that these GO pathways are associated with PPROM and yellow labels were not detected from PPROM in this study. The order of the number represents the p value for how significant it is associated with PPROM.

Bottom Line: Our results showed that 22 pathways were characterized as up-regulated 7 down-regulated in A vs.C, 18 up-regulated and 15 down-regulated in A vs.D, and 33 up-regulated and 7 down-regulated in A vs.

View Article: PubMed Central - PubMed

Affiliation: Center of Translational Medicine for Maternal and Children's Health, Lianyungang Maternal and Children's Hospital, Lianyungang, Jiangsu, China.

ABSTRACT
Preterm birth (PTB) is a live birth delivered before 37 weeks of gestation (GW). About one-third of PTBs result from the preterm premature rupture of membranes (PPROM). Up to the present, the pathogenic mechanisms underlying PPROM are not clearly understood. Here, we investigated the differential expression of long chain non-coding RNAs (lncRNAs) in placentas of PTBs with PPROM, and their possible involvement in the pathogenic pathways leading to PPROM. A total number of 1954, 776, and 1050 lncRNAs were identified with a microarray from placentas of PPROM (group A), which were compared to full-term birth (FTB) (group B), PTB (group C), and premature rupture of membrane (PROM) (group D) at full-term, respectively. Instead of investigating the individual pathogenic role of each lncRNA involved in the molecular mechanism underlying PPROM, we have focused on investigating the metabolic pathways and their functions to explore what is the likely association and how they are possibly involved in the development of PPROM. Six groups, including up-regulation and down-regulation in the comparisons of A vs. B, A vs. C, and A vs. D, of pathways were analyzed. Our results showed that 22 pathways were characterized as up-regulated 7 down-regulated in A vs. C, 18 up-regulated and 15 down-regulated in A vs. D, and 33 up-regulated and 7 down-regulated in A vs. B. Functional analysis showed pathways of infection and inflammatory response, ECM-receptor interactions, apoptosis, actin cytoskeleton, and smooth muscle contraction are the major pathogenic mechanisms involved in the development of PPROM. Characterization of these pathways through identification of lncRNAs opened new avenues for further investigating the epigenomic mechanisms of lncRNAs in PPROM as well as PTB.

Show MeSH
Related in: MedlinePlus