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Hsa_circ_0001326 regulates proliferation, migration, invasion, and EMT of HTR-8/SVneo cells via increasing IL16 expression

Am J Reprod Immunol. 2021 Nov;86(5):e13484. doi: 10.1111/aji.13484. Epub 2021 Jul 22.

Abstract

Background: Preeclampsia (PE) is a serious pregnancy complication. It has been shown that insufficient infiltration of extravillous trophoblasts (EVTs) is related to the pathogenesis of PE. Circular hsa_circ_0001326 (circ_0001326) has been uncovered to be upregulated in PE. However, the influence of circ_0001326 on the infiltration of trophoblasts is indistinct.

Methods: 48 pregnant women (25 PE patients and 23 healthy controls) were recruited for this study. Human trophoblasts HTR-8/Svneo were used for function analysis. Expression of circ_0001326 was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). The diagnostic value of circ_0001326 was analyzed by receiver operating characteristic (ROC) curve. Cell proliferation, migration, and invasion of HTR-8/Svneo cells were determined using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), wound-healing, and transwell assays. Protein levels were detected using Western blotting. The regulation mechanism of circ_0001326 was surveyed by bioinformatics analysis and dual-luciferase reporter assay.

Results: Circ_0001326 was highly expressed in plasma samples and placental tissues of PE patients. Moreover, plasma circ_0001326 could distinguish PE patients from healthy controls (area under the curve (AUC) =0.793). Functionally, circ_0001326 overexpression repressed HTR-8/Svneo cell proliferation, epithelial-mesenchymal transition (EMT), migration, and invasion, but circ_0001326 silencing had the opposing impact. Mechanically, circ_0001326 regulated interleukin-16 (IL16) expression via sponging microRNA (miR)-558. MiR-558 mimic or IL16 knockdown overturned the inhibiting effect of circ_0001326 overexpression on HTR-8/Svneo cell proliferation, EMT, migration, and invasion.

Conclusion: Circ_0001326 elevated IL16 expression via sponging miR-558, thus curbing HTR-8/Svneo cell proliferation, EMT, migration, and invasion, suggesting that circ_0001326 might be involved in the pathogenesis of PE.

Keywords: HTR-8/Svneo; IL16; circ_0001326; miR-558; preeclampsia.

MeSH terms

  • Case-Control Studies
  • Cell Line
  • Cell Movement*
  • Cell Proliferation*
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Interleukin-16 / genetics
  • Interleukin-16 / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Pre-Eclampsia / genetics
  • Pre-Eclampsia / metabolism*
  • Pre-Eclampsia / pathology
  • Pregnancy
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Signal Transduction
  • Trophoblasts / metabolism*
  • Trophoblasts / pathology
  • Up-Regulation

Substances

  • Il16 protein, human
  • Interleukin-16
  • MIRN-558 microRNA, human
  • MicroRNAs
  • RNA, Circular