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EBF1-Correlated Long Non-coding RNA Transcript Levels in 3rd Trimester Maternal Blood and Risk of Spontaneous Preterm Birth

  • Reproductive Epidemiology: Original Article
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Abstract

Biomarkers associated with spontaneous preterm birth (sPTB) before labor onset could aid in prediction, triage, and stratification for testing interventions. In this study we examined maternal blood EBF1-correlated long non-coding RNAs (lncRNAs) in relation to sPTB. We retrieved all lncRNA transcripts from a public gene expression dataset (GSE59491) derived from maternal blood in trimesters 2 and 3 from a Canadian cohort with a matched set of sPTB (n = 51) and term births (n = 106). LncRNA transcripts differentially expressed (limma moderated t-tests) in sPTB vs. term were tested for correlations (Pearson) with EBF1 mRNA levels in the same blood samples. Using logistic regression, EBF1-correlated lncRNAs were divided into tertiles and assessed in relation to odds of sPTB. Two lncRNA transcripts in the 3rd trimester maternal blood were differentially expressed between sPTB and term births (all p < 0.001 and FDR < 0.250) and positively and negatively correlated with EBF1 mRNA levels. They were as follows: (1) LINC00094 r = 0.196 (95% CI: 0.039 to 0.344), p = 0.015, and BH adjusted p = 0.022 and (2) LINC00870 r = − 0.303 (95% CI: − 0.441 to − 0.152), p < 0.001, and BH adjusted p < 0.001. As compared with term births, sPTBs were more likely to be in the highest tertile of LINC00870 (odds ratio (OR) = 4.08 (95% CI 1.60, 10.40), p = 0.003) and the lowest tertile of LINC00094 (OR = 5.16 (95% CI 1.96, 13.61), p < 0.001). Two sPTB-associated EBF1-correlated lncRNAs (LINC00870 and LINC00094) had multiple potential enhancers containing EBF1 binding site(s). Our current findings, along with previous reports linking EBF1 and sPTB, motivate additional research on the EBF1 gene-related gene expression and regulation in relation to sPTB within other cohorts and within laboratory-based models.

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Authors and Affiliations

  1. Clinical & Translational Sciences Institute, Michigan State University, East Lansing, MI, USA

    Guoli Zhou & Eric P. Kasten

  2. Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA

    Claudia Holzman

  3. Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI, USA

    Bin Chen

  4. Precision Health Program, Michigan State University, East Lansing, MI, USA

    Ping Wang

  5. Department of Radiology, Michigan State University, East Lansing, MI, USA

    Ping Wang & Eric P. Kasten

  6. Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Yujing J. Heng

  7. Departments of Obstetrics & Gynaecology and Physiology, University of Toronto, Toronto, ON, Canada

    Mark Kibschull & Stephen J. Lye

  8. Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada

    Mark Kibschull & Stephen J. Lye

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Contributions

G.Z. developed research ideas, conducted data analyses including statistical analysis and bioinformatics analysis, interpreted the data, and drafted manuscript. C.H. provided advice on developing research ideas and conducting data analyses, interpreted the data, as well as reviewed and revised manuscript. B.C., P.W., Y.J.H, M.K., S.J.L., and E.K. reviewed and revised manuscript. All authors gave final approval of the version to be published.

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Correspondence to Guoli Zhou.

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Zhou, G., Holzman, C., Chen, B. et al. EBF1-Correlated Long Non-coding RNA Transcript Levels in 3rd Trimester Maternal Blood and Risk of Spontaneous Preterm Birth. Reprod. Sci. 28, 541–549 (2021). https://doi.org/10.1007/s43032-020-00320-5

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