Di-san junyi daxue xuebao (Nov 2020)

LncRNA HIF1A-AS2 promotes trophoblast invasion and epithelial-mesenchymal transformation by inhibiting miR-138-5p

  • LI Qin,
  • XU Juanxiu,
  • YAO Xuan

DOI
https://doi.org/10.16016/j.1000-5404.202006084
Journal volume & issue
Vol. 42, no. 22
pp. 2210 – 2218

Abstract

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Objective To investigate the effect and underlying mechanism of long non-coding RNA (lncRNA) hypoxia-inducible factor 1 alpha antisense RNA 2 (HIF1A-AS2) on trophoblast invasion and epithelial-mesenchymal transition (EMT). Methods The mRNA levels of HIF1A-AS2 and its predicted targering miR-138-5p in the placental tissues of preeclampsia (PE) patients (PE group, n=20) and normal placental tissues (control group, n=20) were detected with qRT-PCR. Human chorionic trophoblast cell line HTR-8/SVneo (epithelial-like cells with adherent growth) were employed to be transfected with HIF1A-AS2 overexpression plasmid, and/or miR-138-5p mimic, miR-138-5p inhibitor as well as theirs corresponding negative controls. Then the cell proliferation, cell invasion and protein expression of EMT-associated molecules (Vimentin and N-cadherin) and EMT-transcription factor (Twist1) were measured by CCK-8 assay, Transwell assay, and Western blotting, respectively. The binding relationship between HIF1A-AS2 and miR-138-5p was verified by luciferase gene reporter assay. Results The mRNA level of HIF1A-AS2 was significantly decreased, while that of miR-138-5p was markedly increased in the PE placental tissues, compared with the normal placental tissues (P < 0.05). Over-expression of HIF1A-AS2 obviously inhibited the expression of miR-138-5p, promoted cell invasion and enhanced the expression of Vimentin, N-cadherin, and Twist1 in the HTR-8/SVneo cells (P < 0.05). The effects of miR-138-5 inhibitor showed similar effects on HTR-8/Svneo cells that of over-expression of HIF1A-AS2, but these effects of the overexpression on HTR-8/Svneo cells could be weakened when miR-138-5p mimic was introduced. Furthermore, the direct bonding between HIF1A-AS2 and miR-138-5p was identified in HTR-8/SVneo cells. Conclusion LncRNA HIF1A-AS2 promotes trophoblast invasion and EMT, which may be fulfilled by its inhibition on the expression of miR-138-5p.

Keywords