LncRNA SNHG1 targets miR-340-5p/PIK3CA axis to regulate microvascular endothelial cell proliferation, migration, and angiogenesis in DR

Kaohsiung J Med Sci. 2023 Jan;39(1):16-25. doi: 10.1002/kjm2.12625. Epub 2022 Dec 9.

Abstract

Diabetic retinopathy (DR) is a serious long-term complication of diabetes. However, the current treatment of DR is still challenging. We aimed to investigate the role of lncRNA SNHG1/miR-340-5p/PIK3CA in DR and the mechanisms involved. Blood samples from clinical DR patients and healthy subjects were obtained. HRMECs were induced by high glucose for 24 h to establish the DR model. The vector for interfering or overexpressing lncRNA SNHG1, miR-340-5p, and PIK3CA was constructed. LncRNA SNHG1, miR-340-5p, and PIK3CA expressions were detected by qRT-PCR or Western blot. Cell proliferation and migration were detected by CCK-8 and Transwell assays. Blood vessel formation was detected by angiogenesis assay. Dual-luciferase reporter assay tested the interaction of lncRNA SNHG1 with miR-340-5p and miR-340-5p with PIK3CA. RIP measured the binding of miR-340-5p to PIK3CA. In the blood of DR patients and the DR model, lncRNA SNHG1 was increased and miR-340-5p expression was down-regulated. In the DR model, PIK3CA expression was elevated. Downregulation of lncRNA SNHG1 inhibited HRMECs proliferation, migration, and angiogenesis. LncRNA SNHG1 interacted with miR-340-5p, and up-regulation of miR-340-5p inhibited HRMECs proliferation, migration and angiogenesis. The inhibition of cell proliferation, migration, and angiogenesis of HRMECs caused by down-regulation of lncRNA SNHG1 was reversed by knockdown of miR-340-5p. miR-340-5p targeted PIK3CA, and downregulation of PIK3CA inhibited HRMECs proliferation, migration, and angiogenesis. The inhibition of HRMECs proliferation, migration and angiogenesis caused by down-regulation of lncRNA SNHG1 could be reversed by overexpression of PIK3CA. LncRNA SNHG1 targeted miR-340-5p/PIK3CA axis to regulate microvascular endothelial cell proliferation, migration, and angiogenesis in DR.

Keywords: PIK3CA; angiogenesis; diabetic retinopathy; lncRNA SNHG1; miR-340-5p.

MeSH terms

  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Class I Phosphatidylinositol 3-Kinases / metabolism
  • Diabetic Retinopathy*
  • Down-Regulation
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • PIK3CA protein, human
  • Class I Phosphatidylinositol 3-Kinases
  • MIRN340 microRNA, human