The lncRNA small nucleolar RNA host gene 5 regulates trophoblast cell proliferation, invasion, and migration via modulating miR‐26a‐5p/N‐cadherin axis

Abstract

Pre-eclampsia (PE) is a pregnancy-specific disease characterized by the occurrence of hypertension and proteinuria after two weeks of gestation. Long noncoding RNAs (lncRNAs) are emerging as key regulators in PE development.This study aims to investigate the role of lncRNA, small nucleolar RNA host gene 5 (SNHG5), in the pathogenesis of PE. The expression of SNHG5 was significantly downregulated in placental tissues from patients with severe PE compared normal controls. Overexpression of SNHG5 promoted trophoblast (HTR-8/SVneo) cell proliferation, invasion, and migration, and flow cytometry results showed that SNHG5 overexpression inhibited apoptosis and caused a decrease of cell population at the G 0 /G 1 phase and an increase of cell population at the S phase, while knockdown of SNHG5 had the opposite effects. The interaction between SNHG5 and miR-26a-5p was predicted by bioinformatics analysis and confirmed by luciferase reporter assay and RNA immunoprecipitation, and miR-26a-5p was negatively regulated by SNHG5; miR-26a-5p expression was upregulated in PE placental tissues and was inversely correlated with SNHG5 expression. Furthermore, miR-26a-5p was predicted to target the 3′ untranslated region of N-cadherin, which was confirmed by luciferase reporter assay, and miR-26a-5p overexpression suppressed N-cadherin expression in HTR-8/SVneo cells. N-cadherin mRNA expression was downregulated in PE placental tissues and was positively correlated with SNHG5 expression.Both overexpression of miR-26a-5p and knockdown of N-cadherin suppressed HTR-8/SVneo cell invasion and migration, and also attenuated the effects of SNHG5 on the cellular functions of HTR-8/SVneo cells. In conclusion, our study suggested that SNHG5 promotes trophoblast cell proliferation, invasion, and migration at least partly via regulating the miR-26a-5p/N-cadherin axis. K E Y W O R D Sinvasion and migration, miR-26a-5p, N-cadherin, pre-eclampsia (PE), small nucleolar RNA host gene 5 (SNHG5), trophoblast J Cell Biochem. 2019;120:3173-3184.wileyonlinelibrary.com/journal/jcb

Long Noncoding RNA in Preeclampsia: Transcriptional Noise or Innovative Indicators?

“…In addition to that, lncRNA‐ATB was manifested to be associated with the incidence of PE by means of the manipulation of the procedure of the cell invasion, coupled with the development of the endothelial vessels [51]. The decline in small nucleolar RNA host gene 5 (SNHG5) in the placentas of PE women indicated that SNHG5 induced not only cell proliferation, but also cell invasion, and migration through the manipulation of the miR‐26a‐5p/N‐cadherin axis [52]. The expression of lncRNA maternally expressed gene 3 (MEG3) in PE placentas was decreased as well [53].…”

Association of lncRNA SH3PXD2A-AS1 with preeclampsia and its function in invasion and migration of placental trophoblast cells

“…H19 inhibits the proliferation of trophoblast cells through encoding miR-675, which down-regulates the expression of NOMO1 54 . SNHG5 is known to promote cancer cell proliferation and survival 56 , and is recently reported to promote the proliferaction, invasion, and migration of trophoblast cells 57 . TUG1 is well documented to promote the proliferation, invasion, and colony formation of cancer cells 58 and trophoblast cells as well 59 .…”

Long non‑coding RNA NR_002794 is upregulated in pre‑eclampsia and regulates the proliferation, apoptosis and invasion of trophoblast cells

“…lncRNAs are capable of regulating the development and metabolism of several cellular activities at the epigenetic, transcriptional and post-transcriptional levels (30). A number of studies have shown that the abnormal expression of lncRNAs in placental tissues during pregnancy is closely related to the onset of pre-eclampsia (31,32). He et al (16) reported that 738 lncRNAs were differentially expressed in the placental tissues of patients with pre-eclampsia, including 479 that were upregulated and 259 that were downregulated.…”