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

Qin LI; Juanxiu XU; Xuan YAO

doi:10.16016/j.1000-5404.202006084

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

Basic Medicine | 更新时间：2026-01-09

- LncRNA HIF1A-AS2 promotes trophoblast invasion and epithelial-mesenchymal transformation by inhibiting miR-138-5p
- Journal of Third Military Medical University Vol. 42, Issue 22, Pages: 2210-2218(2020)
- 作者机构：
  
  1.330006 南昌，江西省妇幼保健院:产科
  2.330006 南昌，江西省妇幼保健院:肿瘤科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.202006084
  CLC： R363.21;R394.3;R714.245
- Received：09 June 2020，
  
  Revised：2020-08-28，
  
  Published：30 November 2020
- 稿件说明：
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Qin LI, Juanxiu XU, Xuan YAO. LncRNA HIF1A-AS2 promotes trophoblast invasion and epithelial-mesenchymal transformation by inhibiting miR-138-5p[J]. Journal of Third Military Medical University, 2020, 42(22): 2210-2218.
DOI：

Qin LI, Juanxiu XU, Xuan YAO. LncRNA HIF1A-AS2 promotes trophoblast invasion and epithelial-mesenchymal transformation by inhibiting miR-138-5p[J]. Journal of Third Military Medical University, 2020, 42(22): 2210-2218. DOI： 10.16016/j.1000-5404.202006084.

摘要

目的

研究长链非编码RNA(long non-coding RNA，lncRNA)缺氧诱导因子-1α-反义链2(hypoxia-inducible factor 1 alpha antisense RNA 2，HIF1A-AS2)对滋养层细胞侵袭和上皮间充质转化(epithelial-mesenchymal transition，EMT)的作用和机制。

方法

比较20个子痫前期(preeclampsia，PE)胎盘(PE组)和20个正常胎盘(对照组)组织中HIF1A-AS2及其预测的靶基因miR-138-5p的表达水平。选用人绒毛膜滋养层细胞系HTR-8/Svneo，在转染HIF1A-AS2过表达质粒、miR-138-5p拟似物和抑制物及各自阴性对照的HTR-8/SVneo细胞中，通过CCK-8检测细胞增殖、Transwell实验检测侵袭、Western blot检测细胞EMT标记分子和转录因子表达来研究HIF1A-AS2和miR-138-5p对滋养层细胞的作用和机制。通过荧光素酶基因报告实验验证HIF1A-AS2和miR-138-5p的结合关系。

结果

PE胎盘中HIF1A-AS2显著降低(

0.05)，而miR-138-5p的表达显著增高(

0.05)。过表达HIF1A-AS2能够抑制miR-138-5p的表达(

0.05)，促进HTR-8/SVneo细胞的侵袭能力(

0.05)，上调EMT标记分子Vimentin和N-cadherin以及EMT转录因子Twist1的表达水平(

0.05)。此外，miR-138-5p抑制物与过表达HIF1A-AS2对HTR-8/SVneo细胞的作用相同，而miR-138-5p拟似物能够减弱过表达HIF1A-AS2对该细胞的作用。另外，HIF1A-AS2和miR-138-5p在HTR-8/Svneo细胞中可以直接结合。

结论

LncRNA HIF1A-AS2能够促进滋养层细胞的侵袭和上皮间充质转化，其作用可能通过抑制miR-138-5p水平来实现。

Abstract

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

=20) and normal placental tissues (control group

=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 (

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 (

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.

关键词

Keywords

references

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