Downregulated MALAT1 relates to recurrent pregnancy loss via sponging miRNAs

Kaohsiung J Med Sci. 2018 Sep;34(9):503-510. doi: 10.1016/j.kjms.2018.04.006. Epub 2018 May 18.

Abstract

Recurrent pregnancy loss (RPL) is three or more times of consecutive spontaneous loss of pregnancy. The underlying cause is complicated and the etiology of over 50% of RPL patients is unclear. Metastasis associated lung adenocarcinoma transcript-1 (MALAT-1), a multiple lncRNA functions as key regulators of diverse cellular processes. In this study, we found a reduced MALAT1 level in the villus samples of 36 RPL patients. Predicted by bioinformatics tool and confirmed by dual luciferase assay, we identified that MALAT1 directly interacts with miRNAs. Subsequent functional study in HTR-8/SVneo and HUVEC cells indicated that MALAT1 modulates the cell proliferation, apoptosis, migration and invasion via directly interact with miR-383, miR-15, miR-205 and miR-375. By modulating the VEGFA expression, MALAT1 controls the capillary formation of HUVEC cells. In conclusion, MALAT1 as a functional lncRNA controls cell proliferation, apoptosis, migration, invasion and modulates blood vessel formation. Down regulated MALAT1 induced disordered cross-talk between embryo and mother is one of the factor contributes to the pathogenesis of RPL.

Keywords: Long non-coding RNA; MALAT1; MicroRNA; Recurrent pregnancy loss.

MeSH terms

  • Abortion, Spontaneous / genetics*
  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Cell Line
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • MicroRNAs / genetics*
  • Pregnancy
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*

Substances

  • MALAT1 long non-coding RNA, human
  • MicroRNAs
  • RNA, Long Noncoding