title: Epigenetic regulation of lncRNA connects ubiquitin-proteasome system with infection-inflammation in preterm births and preterm premature rupture of membranes.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Here, 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  Differentially 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.
authors.affiliation: Center of Translational Medicine for Maternal and Children's Health, Lianyungang Maternal and Children's Hospital, Lianyungang, Jiangsu, China. lxc8816@sina.com.|Chinese Alliance of Translational Medicine for Maternal and Children's Health, Beijing, China. lxc8816@sina.com.
authors.forename: Xiucui
authors.initials: X
authors.lastname: Luo
authors.affiliation: Center of Translational Medicine for Maternal and Children's Health, Lianyungang Maternal and Children's Hospital, Lianyungang, Jiangsu, China. lygkjk@126.com.|Chinese Alliance of Translational Medicine for Maternal and Children's Health, Beijing, China. lygkjk@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.affiliation: Center of Translational Medicine for Maternal and Children's Health, Lianyungang Maternal and Children's Hospital, Lianyungang, Jiangsu, China. wangleileiok@hotmail.com.
authors.forename: Leilei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Center of Translational Medicine for Maternal and Children's Health, Lianyungang Maternal and Children's Hospital, Lianyungang, Jiangsu, China. wangpeirong@gmail.com.|Peking University Center of Medical Genetics, Beijing, China. wangpeirong@gmail.com.|Chinese Alliance of Translational Medicine for Maternal and Children's Health, Beijing, China. wangpeirong@gmail.com.
authors.forename: Peirong
authors.initials: P
authors.lastname: Wang
authors.affiliation: Center of Translational Medicine for Maternal and Children's Health, Lianyungang Maternal and Children's Hospital, Lianyungang, Jiangsu, China. 940651562@qq.com.
authors.forename: Meijiao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Center of Translational Medicine for Maternal and Children's Health, Lianyungang Maternal and Children's Hospital, Lianyungang, Jiangsu, China. 591453886@qq.com.
authors.forename: Meilin
authors.initials: M
authors.lastname: Liu
authors.affiliation: Center of Translational Medicine for Maternal and Children's Health, Lianyungang Maternal and Children's Hospital, Lianyungang, Jiangsu, China. qingqing-dzq@126.com.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Center of Translational Medicine for Maternal and Children's Health, Lianyungang Maternal and Children's Hospital, Lianyungang, Jiangsu, China. lygmq6326@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Center of Translational Medicine for Maternal and Children's Health, Lianyungang Maternal and Children's Hospital, Lianyungang, Jiangsu, China. xgtltw2005@gmail.com.|Peking University Center of Medical Genetics, Beijing, China. xgtltw2005@gmail.com.|Chinese Alliance of Translational Medicine for Maternal and Children's Health, Beijing, China. xgtltw2005@gmail.com.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Tao
authors.affiliation: Center of Translational Medicine for Maternal and Children's Health, Lianyungang Maternal and Children's Hospital, Lianyungang, Jiangsu, China. xinliang.zhao@gmail.com.|Peking University Center of Medical Genetics, Beijing, China. xinliang.zhao@gmail.com.|Chinese Alliance of Translational Medicine for Maternal and Children's Health, Beijing, China. xinliang.zhao@gmail.com.
authors.forename: Xinliang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Center of Translational Medicine for Maternal and Children's Health, Lianyungang Maternal and Children's Hospital, Lianyungang, Jiangsu, China. Julia.zhong1@gmail.com.|Hunter College High School, New York, USA. Julia.zhong1@gmail.com.
authors.forename: Julia
authors.initials: J
authors.lastname: Zhong
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA. weina.ju@yahoo.com.
authors.forename: Weina
authors.initials: W
authors.lastname: Ju
authors.affiliation: Center of Translational Medicine for Maternal and Children's Health, Lianyungang Maternal and Children's Hospital, Lianyungang, Jiangsu, China. 815501606@qq.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gu
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA. ed.jenkins@opwdd.ny.gov.
authors.forename: Edmund C
authors.initials: EC
authors.lastname: Jenkins
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA. Ted.brown@opwdd.ny.gov.
authors.forename: W Ted
authors.initials: WT
authors.lastname: Brown
authors.affiliation: Center of Translational Medicine for Maternal and Children's Health, Lianyungang Maternal and Children's Hospital, Lianyungang, Jiangsu, China. shiqingxi0220@163.com.|Chinese Alliance of Translational Medicine for Maternal and Children's Health, Beijing, China. shiqingxi0220@163.com.
authors.forename: Qingxi
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Center of Translational Medicine for Maternal and Children's Health, Lianyungang Maternal and Children's Hospital, Lianyungang, Jiangsu, China. nanbert.zhong@opwdd.ny.gov.|New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA. nanbert.zhong@opwdd.ny.gov.|Peking University Center of Medical Genetics, Beijing, China. nanbert.zhong@opwdd.ny.gov.|Children's Hospital of Shanghai Affiliated to Shanghai Jiaotong University, Shanghai, China. nanbert.zhong@opwdd.ny.gov.|Chinese Alliance of Translational Medicine for Maternal and Children's Health, Beijing, China. nanbert.zhong@opwdd.ny.gov.|March of Dimes Global Network of Maternal and Infant Health, March of Dimes Foundation, White Plains, USA. nanbert.zhong@opwdd.ny.gov.|Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY, 10314, USA. nanbert.zhong@opwdd.ny.gov.
authors.forename: Nanbert
authors.initials: N
authors.lastname: Zhong
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D015536:Down-Regulation; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000235:genetics / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010750:Phosphoproteins / Q000235:genetics; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D010750:Phosphoproteins; D062085:RNA, Long Noncoding; C109775:STAM protein, human; C410333:TACC2 protein, human; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin; C503981:PPP2R5C protein, human; D054648:Protein Phosphatase 2; D046988:Proteasome Endopeptidase Complex