Abstract
BackgroundPreterm premature rupture of membranes (PPROM) is responsible for one third of all preterm births (PTBs). We have recently demonstrated that long noncoding RNAs (lncRNAs) are differentially expressed in human placentas derived from PPROM, PTB, premature rupture of the membranes (PROM), and full-term birth (FTB), and determined the major biological pathways involved in PPROM.MethodsHere, we further investigated the relationship of lncRNAs, which are differentially expressed in spontaneous PTB (sPTB) and PPROM placentas and are found to overlap a coding locus, with the differential expression of transcribed mRNAs at the same locus. Ten lncRNAs (five up-regulated and five down-regulated) and the lncRNA-associated 10 mRNAs (six up- and four down-regulated), which were identified by microarray in comparing PPROM vs. sPTB, were then validated by real-time quantitative PCR.ResultsA total of 62 (38 up- and 24 down-regulated) and 1,923 (790 up- and 1,133 down-regulated) lncRNAs were identified from placentas of premature labor (sPTB + PPROM), as compared to those from full-term labor (FTB + PROM) and from premature rupture of membranes (PPROM + PROM), as compared to those from non-rupture of membranes (sPTB + FTB), respectively. We found that a correlation existed between differentially expressed lncRNAs and their associated mRNAs, which could be grouped into four categories based on the gene strand (sense or antisense) of lncRNA and its paired transcript. These findings suggest that lncRNA regulates mRNA transcription through differential mechanisms. Differential expression of the transcripts PPP2R5C, STAM, TACC2, EML4, PAM, PDE4B, STAM, PPP2R5C, PDE4B, and EGFR indicated a co-expression among these mRNAs, which are involved in the ubiquitine-proteasome system (UPS), in addition to signaling transduction and beta adrenergic signaling, suggesting that imbalanced regulation of UPS may present an additional mechanism underlying the premature rupture of membrane in PPROM.ConclusionDifferentially expressed lncRNAs that were identified from the human placentas of sPTB and PPROM may regulate their associated mRNAs through differential mechanisms and connect the ubiquitin-proteasome system with infection-inflammation pathways. Although the detailed mechanisms by which lncRNAs regulate their associated mRNAs in sPTB and PPROM are yet to be clarified, our findings open a new approach to explore the pathogenesis of sPTB and PPROM.
Highlights
Preterm premature rupture of membranes (PPROM) is responsible for one third of all preterm births (PTBs)
Placentas A total of 40 placentas from age-matched pregnant women (25–30 years old) were divided into four groups of deliveries (10 placentas per group): spontaneous PTB (sPTB), full-term birth (FTB), PPROM, and premature rupture of the membranes (PROM), labeled as group A, B, C, and D, respectively. sPTB is defined as birth delivered at < 35 (= < 34+6) GW without premature rupture of amniochorionic membrane (PROM), FTB is defined as birth delivered at 39–40+6 GW without PROM; PPROM is defined as birth delivered at < 35 (= < 34+6) GW with PROM; and PROM is defined as birth delivered at 39–40+6 GW with premature rupture of the amniochorionic membrane before labor, which is the contraction of the uterus
Identification of differentially expressed long noncoding RNAs (lncRNAs) in comparisons of group AC (PTB & PPROM) vs. group BD (FTB & PROM) and group CD (PPROM & PROM) vs. group AB (PTB & FTB) Differential expression was both up- and down-regulated
Summary
Preterm premature rupture of membranes (PPROM) is responsible for one third of all preterm births (PTBs). We have recently demonstrated that long noncoding RNAs (lncRNAs) are differentially expressed in human placentas derived from PPROM, PTB, premature rupture of the membranes (PROM), and full-term birth (FTB), and determined the major biological pathways involved in PPROM. Preterm premature rupture of membranes (PPROM), which occurs in one-third of all preterm births (PTBs), is one of the major causes of prematurity [1]. It accounts for a disproportionate amount of perinatal morbidity and mortality [2,3]. MiRNAs, the most widely studied class of short ncRNAs, mediate post-transcriptional gene silencing by controlling the translation of mRNA into protein [13,14] and are involved in regulating proliferation, differentiation, apoptosis, and development [15]. The disruption of other classes of short ncRNAs, such as small nucleolar
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