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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

Validation of lncRNAs.RT-qPCR was applied to validate differentially expressed lncRNAs between the PPROM and PTB. Seven up-regulated lncRNAs (A) and nine down-regulated ones (B) were analyzed. Other than the sequence name, each lncRNA was labeled with its associated gene accession in GenBank for a purpose of easy access to its associated gene. Significant levels were indicated by * (p<0.05) and ** (p<0.01).
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pone-0079897-g002: Validation of lncRNAs.RT-qPCR was applied to validate differentially expressed lncRNAs between the PPROM and PTB. Seven up-regulated lncRNAs (A) and nine down-regulated ones (B) were analyzed. Other than the sequence name, each lncRNA was labeled with its associated gene accession in GenBank for a purpose of easy access to its associated gene. Significant levels were indicated by * (p<0.05) and ** (p<0.01).

Mentions: Seven up-regulated and nine down-regulated lncRNAs in PPROM (group A) compared with PTB (group C) in microarray assay (Table 2) were randomly chosen for validation, using a technology of real-time quantitative PCR (RT-qPCR). The results revealed that all the up-regulated lncRNAs were increased in PPROM compared to PTB, and six of them rose significantly (Figure 2A). As well, all the down-regulated ones were decreased in PPROM, and eight of them declined significantly (Figure 2B). Therefore, the results of the qPCR analysis were consistent with those of the microarray.


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)

Validation of lncRNAs.RT-qPCR was applied to validate differentially expressed lncRNAs between the PPROM and PTB. Seven up-regulated lncRNAs (A) and nine down-regulated ones (B) were analyzed. Other than the sequence name, each lncRNA was labeled with its associated gene accession in GenBank for a purpose of easy access to its associated gene. Significant levels were indicated by * (p<0.05) and ** (p<0.01).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0079897-g002: Validation of lncRNAs.RT-qPCR was applied to validate differentially expressed lncRNAs between the PPROM and PTB. Seven up-regulated lncRNAs (A) and nine down-regulated ones (B) were analyzed. Other than the sequence name, each lncRNA was labeled with its associated gene accession in GenBank for a purpose of easy access to its associated gene. Significant levels were indicated by * (p<0.05) and ** (p<0.01).
Mentions: Seven up-regulated and nine down-regulated lncRNAs in PPROM (group A) compared with PTB (group C) in microarray assay (Table 2) were randomly chosen for validation, using a technology of real-time quantitative PCR (RT-qPCR). The results revealed that all the up-regulated lncRNAs were increased in PPROM compared to PTB, and six of them rose significantly (Figure 2A). As well, all the down-regulated ones were decreased in PPROM, and eight of them declined significantly (Figure 2B). Therefore, the results of the qPCR analysis were consistent with those of the microarray.

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