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.
References
[1]
Romero R, Friel LA, Velez Edwards DR, Kusanovic JP, Hassan SS, et al. (2010) A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM). Am J Obstet Gynecol 203: 361.e1–361.e330 (doi: 10.1016/j.ajog.2010.05.026).
[2]
Lawn J, Gravett M, Nunes T, Rubens C, Stanton C (2010) Global report on preterm birth and stillbirth (1 of 7): definitions, description of the burden and opportunities to improve data. BMC Pregnancy Childb 10: S1 DOI:10.1186/1471-2393-10-S1-S1.
[3]
Srinivas S, Macones G (2005) Preterm premature rupture of the fetal membranes: current concepts. Minerva ginecologica 57: 389.
[4]
DeFranco E, Teramo K, Muglia L (2007) Genetic influences on preterm birth. Thieme. pp. 40.
[5]
Menon R, Fortunato SJ (2007) Infection and the role of inflammation in preterm premature rupture of the membranes. Best Practice & Res Clin Obstet & Gynaecol. 21: 467.
[6]
Romero R, Yoon BH, Mazor M, Gomez R, Diamond MP, et al. (1993) The diagnostic and prognostic value of amniotic fluid white blood cell count, glucose, interleukin-6, and gram stain in patients with preterm labor and intact membranes. Am J Obstet Gynecol. 169: 805–816.
[7]
Romero R GF, Mazaki-Tovi S, Kusanovic JP (2010) Inflammation and infection. In: Berghella V, editor. Preterm Birth. Blackwell Publishing.
[8]
Behrman RE, Butler AS (2007) Preterm birth: causes, consequences, and prevention: National Academy Press.
[9]
Menon R, Fortunato SJ (2004) Preterm premature rupture of the membrane: A network of MMPs and apoptosis. J Soc Gynecol Invest. 11: 427–437.
[10]
Plunkett J, Doniger S, Orabona G, Morgan T, Haataja R, et al. (2011) An evolutionary genomic approach to identify genes involved in human birth timing. PLOS Genet. 7: e1001365.
[11]
Kalish RB, Vardhana S, Normand NJ, Gupta M, Witkin SS (2006) Association of a maternal CD14 -159 gene polymorphism with preterm premature rupture of membranes and spontaneous preterm birth in multi-fetal pregnancies. J Reprod Immunol. 70: 109–117.
[12]
Valdez-Velazquez LL, Quintero-Ramos A, Perez SA, Mendoza-Carrera F, Montoya-Fuentes H, et al. (2007) Genetic polymorphisms of the renin-angiotensin system in preterm delivery and premature rupture of membranes. J Renin-Angiotensin-Aldosterone System 8: 160–168.
[13]
Ferrand PE, Fujimoto T, Chennathukuzhi V, Parry S, Macones GA, et al. (2002) The CARD15 2936insC mutation and TLR4 896 A>G polymorphism in African Americans and risk of preterm premature rupture of membranes (PPROM). Mol Hum Reprod. 8: 1031–1034.
[14]
Salminen A, Paananen R, Karjalainen MK, Tuohimaa A, Luukkonen A, et al. (2009) Genetic association of SP-C with duration of preterm premature rupture of fetal membranes and expression in gestational tissues. Ann Med. 41: 629–642.
[15]
Roberts AK, Monzon-Bordonaba F, Van Deerlin PG, Holder J, Macones GA, et al. (1999) Association of polymorphism within the promoter of the tumor necrosis factor α gene with increased risk of preterm premature rupture of the fetal membranes. AmJ Obstet Gynecol. 180: 1297–1302.
[16]
Fortunato SJ, Menon R, Lombardi SJ (2002) Role of tumor necrosis factor-alpha in the premature rupture of membranes and preterm labor pathways. Am J Obstet Gynecol. 187: 1159–1162.
[17]
Kalish RB, Vardhana S, Gupta M, Perni SC, Chasen ST, et al. (2004) Polymorphisms in the tumor necrosis factor-α gene at position？ 308 and the inducible 70 kd heat shock protein gene at position+1267 in multifetal pregnancies and preterm premature rupture of fetal membranes. Am J Obstet Gynecol. 191: 1368–1374.
[18]
Fuks A, Parton LA, Polavarapu S, Netta D, Strassberg S, et al. (2005) Polymorphism of Fas and Fas ligand in preterm premature rupture of membranes in singleton pregnancies. Am J Obstet Gynecol. 193: 1132–1136.
[19]
？ukaszewski T, Barlik M, Seremak-Mrozikiewicz A, Kurzawińska G, Mrozikiewicz P, et al. (2009) [Polymorphism in the genes of Toll-like receptors type 2 and type 4 (TLR-2 and TLR-4) and the risk of premature rupture of the membranes—preliminary study]. Ginekologia polska 80: 914.
[20]
Rey G, Skowronek F, Alciaturi J, Alonso J, Bertoni B, et al. (2008) Toll receptor 4 Asp299Gly polymorphism and its association with preterm birth and premature rupture of membranes in a South American population. Mol Hum Reprod. 14: 555–559.
[21]
Moseley ML, Zu T, Ikeda Y, Gao W, Mosemiller AK, et al. (2006) Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8. Nat Genet. 38: 758–769.
[22]
Shore AN, Kabotyanski EB, Roarty K, Smith MA, Zhang Y, et al. (2012) Pregnancy-Induced Noncoding RNA (PINC) Associates with Polycomb Repressive Complex 2 and Regulates Mammary Epithelial Differentiation. PLOS Genet. 8: e1002840.
[23]
Dermitzakis ET, Reymond A, Antonarakis SE (2005) Conserved non-genic sequences—an unexpected feature of mammalian genomes. Nat Rev Genet. 6: 151–157.
[24]
Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, et al. (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316: 1484–1488.
[25]
Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS (2010) Non-coding RNAs: regulators of disease. J Pathol. 220: 126–139.
[26]
Wilusz JE, Sunwoo H, Spector DL (2009) Long noncoding RNAs: functional surprises from the RNA world. Genes Dev. 23: 1494–1504.
[27]
Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet. 10: 155–159.
[28]
Gibb EA, Brown CJ, Lam WL (2011) The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 10: 38.
[29]
Koerner MV, Pauler FM, Huang R, Barlow DP (2009) The function of non-coding RNAs in genomic imprinting. Development 136: 1771–1783.
[30]
Tripathi V, Ellis JD, Shen Z, Song DY, Pan Q, et al. (2010) The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell 39: 925–938.
[31]
Feng J, Bi C, Clark BS, Mady R, Shah P, et al. (2006) The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. Genes Dev 20: 1470–1484.
[32]
Willingham A, Orth A, Batalov S, Peters E, Wen B, et al. (2005) A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science Signalling 309: 1570.
[33]
Clemson CM, Hutchinson JN, Sara SA, Ensminger AW, Fox AH, et al. (2009) An Architectural Role for a Nuclear Noncoding RNA: RNA Is essential for the structure of paraspeckles. Mol Cell 33: 717–726.
[34]
Wapinski O, Chang HY (2011) Long noncoding RNAs and human disease. Trends Cell Biol. 21: 354–361.
[35]
Tsai M-C, Spitale RC, Chang HY (2011) Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res. 71: 3–7.
[36]
Mitchell Guttman IA, Garber M, French C, Lin MF, Feldser D, et al. (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458: 223–227.
[37]
Hung T, Wang Y, Lin MF, Koegel AK, Kotake Y, et al. (2011) Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nature genetics 43: 621–629.
[38]
Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, et al. (2010) A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142: 409–419.
[39]
Pasmant E, Laurendeau I, Héron D, Vidaud M, Vidaud D, et al. (2007) Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF. Cancer Res. 67: 3963–3969.
[40]
Pasmant E, Sabbagh A, Masliah-Planchon J, Ortonne N, Laurendeau I, et al. (2011) Role of noncoding RNA ANRIL in genesis of plexiform neurofibromas in neurofibromatosis type 1. J Nat Cancer Inst. 103: 1713–1722.
[41]
Iacobucci I, Sazzini M, Garagnani P, Ferrari A, Boattini A, et al. (2011) A polymorphism in the chromosome 9p21 locus is associated to Philadelphia positive acute lymphoblastic leukemia. Leukemia Res. 35: 1052–1059.
[42]
Yap KL, Li S, Mu？oz-Cabello AM, Raguz S, Zeng L, et al. (2010) Molecular Interplay of the Noncoding RNA and Methylated Histone H3 Lysine 27 by Polycomb CBX7 in Transcriptional Silencing of INK4a. Mol Cell 38: 662–674.
[43]
Yang Z, Zhou L, Wu L-M, Lai M-C, Xie H-Y, et al. (2011) Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Onc. 18: 1243–1250.
[44]
Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, et al. (2011) Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 71: 6320–6326.
[45]
Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, et al. (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464: 1071–1076.
[46]
Scheele C, Nielsen AR, Walden TB, Sewell DA, Fischer CP, et al. (2007) Altered regulation of the PINK1 locus: a link between type 2 diabetes and neurodegeneration? FASEB 21: 3653–3665.
[47]
Berteaux N, Aptel N, Cathala G, Genton C, Coll J, et al. (2008) A novel H19 antisense RNA overexpressed in breast cancer contributes to paternal IGF2 expression. Science Signalling 28: 6731.
[48]
Crosthwaite SK (2004) Circadian clocks and natural antisense RNA. FEBS let 567: 49–54.
[49]
Dreesen TD, Adamson AW, Tekle M, Tang C, Cho HP, et al. (2006) A newly discovered member of the fatty acid desaturase gene family: a non-coding, antisense RNA gene to delta5-desaturase. Prostaglandins Leukot Essent Fatty Acids 75: 97–106.
[50]
Castillo AF, Fan J, Papadopoulos V, Podestá EJ (2011) Hormone-dependent expression of a steroidogenic acute regulatory protein natural antisense transcript in MA-10 mouse tumor Leydig cells. PLOS One 6: e22822.
[51]
Faghihi MA, Wahlestedt C (2009) Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol. 10: 637–643.
[52]
Annilo T, Kepp K, Laan M (2009) Natural antisense transcript of natriuretic peptide precursor A (NPPA): structural organization and modulation of NPPA expression. BMC Mol Biol. 10: 81.
[53]
Kino T, Hurt DE, Ichijo T, Nader N, Chrousos GP (2010) Noncoding RNA gas5 is a growth arrest-and starvation-associated repressor of the glucocorticoid receptor. Science Signalling 3: ra8.
[54]
Khachane AN, Harrison PM (2010) Mining mammalian transcript data for functional long non-coding RNAs. PLOS One 5: e10316.
[55]
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, et al. (2003) Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet 36: 40–45.
[56]
Okazaki Y, Furuno M, Kasukawa T, Adachi J, Bono H, et al. (2002) Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature 420: 563–573.
[57]
Tupy JL, Bailey AM, Dailey G, Evans-Holm M, Siebel CW, et al. (2005) Identification of putative noncoding polyadenylated transcripts in Drosophila melanogaster. PNAS USA. 102: 5495–5500.
[58]
Wang KC, Chang HY (2011) Molecular mechanisms of long noncoding RNAs. Mol Cell 43: 904–914.
[59]
Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136: 629–641.
[60]
Erez O, Romero R, Tarca AL, Chaiworapongsa T, Kim YM, et al. (2009) Differential expression pattern of genes encoding for anti-microbial peptides in the fetal membranes of patients with spontaneous preterm labor and intact membranes and those with preterm PROM. J Matern-Fetal Neo Med. 22: 1103–1115 (doi: 10.3109/14767050902994796)..
[61]
Gomez-Lopez N, Laresgoiti-Servitje E, Olson DM, Estrada-Gutierrez G, Vadillo-Ortega F (2010) The Role of Chemokines in Term and Premature Rupture of the Fetal Membranes: A Review. Biol Reprod. 82: 809–814.
[62]
Menon R, Fortunato SJ (2007) Infection and the role of inflammation in preterm premature rupture of the membranes. Best Pract Res Clin Obstet Gynaecol. 21: 467–478.
[63]
Hanada T, Yoshimura A (2002) Regulation of cytokine signaling and inflammation. Cyto Growth Fact Rev. 13: 413.
[64]
Menon R, Fortunato SJ (2004) The role of matrix degrading enzymes and apoptosis in rupture of membranes. J Soc Gynecol Invest 11: 427–437.
[65]
Kamada S, Kikkawa U, Tsujimoto Y, Hunter T (2005) A-kinase-anchoring protein 95 functions as a potential carrier for the nuclear translocation of active caspase 3 through an enzyme-substrate-like association. Mol Cell Biol 25: 9469–9477.
[66]
Morel C, Adami P, Musard JF, Duval D, Radom J, et al. (2007) Involvement of sulfhydryl oxidase QSOX1 in the protection of cells against oxidative stress-induced apoptosis. Exp Cell Res. 313: 3971–3982.
[67]
Yoshikawa H, Nagashima M, Khan MA, McMenamin MG, Hagiwara K, et al. (1999) Mutational analysis of p73 and p53 in human cancer cell lines. Oncogene 18: 3415–3421.
[68]
Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, et al. (1997) Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell 90: 809–819.
[69]
Loechel F, Gilpin BJ, Engvall E, Albrechtsen R, Wewer UM (1998) Human ADAM 12 (meltrin alpha) is an active metalloprotease. JBC. 273: 16993–16997.
[70]
Kveiborg M, Albrechtsen R, Couchman JR, Wewer UM (2008) Cellular roles of ADAM12 in health and disease. Int J Biochem Cell Biol. 40: 1685–1702 doi: 10.1016/j.biocel.2008.01.025.
[71]
Maglione D, Guerriero V, Viglietto G, Delli-Bovi P, Persico MG (1991) Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. PNAS USA. 88: 9267–9271.
