Mechanism of LEF1-AS1 regulating HUVEC cells by targeting miR-489-3p/S100A11 axis

PeerJ. 2023 Nov 1:11:e16128. doi: 10.7717/peerj.16128. eCollection 2023.


Background: The venous malformation is the most common congenital vascular malformation and exhibits the characteristics of local invasion and lifelong progressive development. Long noncoding RNA (lncRNA) regulates endothelial cells, vascular smooth muscle cells, macrophages, vascular inflammation, and metabolism and also affects the development of venous malformations. This study aimed to elucidate the role of the lncRNA LEF1-AS1 in the development of venous malformations and examine the interaction among LEF1-AS1, miR-489-3p, and S100A11 in HUVEC cells.

Methods: Venous malformation tissues, corresponding normal venous tissues, and HUVEC cells were used. Agilent human lncRNA microarray gene chip was used to screen differential genes, RNA expression was detected using quantitative reverse transcription PCR, and protein expression was detected using Western blotting. The proliferation, migration, and angiogenesis of HUVEC cells were assessed using CCK8, transwell, and in vitro angiogenesis tests.

Results: A total of 1,651 lncRNAs were screened using gene chip analysis, of which 1015 were upregulated and 636 were downregulated. The lncRNA LEF1-AS1 was upregulated with an obvious difference multiple, and the fold-change value was 11.03273. The results of the analysis performed using the StarBase bioinformatics prediction website showed that LEF1-AS1 and miR-489-3p possessed complementary binding sites and that miR-489-3p and S100A11 also had complementary binding sites. The findings of tissue experiments revealed that the expressions of LEF1-AS1 and S100A11 were higher in tissues with venous malformations than in normal tissues, whereas the expression of miR-489-3p was lower in venous malformations than in normal tissues. Cell culture experiments indicated that LEF1-AS1 promoted the proliferation, migration, and angiogenesis of HUVEC cells. In these cells, LEF1-AS1 targeted miR-489-3p, which in turn targeted S100A11. LEF1-AS1 acted as a competitive endogenous RNA and promoted the expression of S100A11 by competitively binding to miR-489-3p and enhancing the proliferation, migration, and angiogenesis of HUVEC cells. Thus, LEF1-AS1 participated in the occurrence and development of venous malformation.

Conclusions: The expression of LEF1-AS1 was upregulated in venous malformations, and the expression of S100A11 was increased by the adsorption of miR-489-3p to venous endothelial cells, thus enhancing the proliferation, migration, and angiogenesis of HUVEC cells. In conclusion, LEF1-AS1 is involved in the occurrence and development of venous malformations by regulating the miR-489-3p/S100A11 axis, which provides valuable insights into the pathogenesis of this disease and opens new avenues for its treatment.

Keywords: HUVEC; LEF1-AS1; S100A11; Venous malformations; miR-489-3p.

MeSH terms

  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Lymphoid Enhancer-Binding Factor 1 / genetics
  • MicroRNAs* / genetics
  • RNA, Antisense* / genetics
  • RNA, Long Noncoding* / genetics
  • S100 Proteins / genetics
  • Vascular Diseases* / genetics


  • LEF1 protein, human
  • Lymphoid Enhancer-Binding Factor 1
  • MicroRNAs
  • MIRN489 microRNA, human
  • RNA, Long Noncoding
  • S100 Proteins
  • S100A11 protein, human
  • RNA, Antisense

Grants and funding

This work was supported by the Special Project of Zhongguancun Precision Medicine Foundation ([2021]018). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.