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Elevated miR‐125b inhibits trophoblast invasion by directly targeting KCNA1 in preeclampsia
Author(s) -
Li Qinghua,
Yin Lingxuan,
Si Yanru,
Meng Yuhan,
Yang Weiwei
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06869
Subject(s) - trophoblast , preeclampsia , placenta , andrology , downregulation and upregulation , microrna , pathogenesis , spiral artery , biology , medicine , pregnancy , endocrinology , chemistry , fetus , gene , genetics
Preeclampsia (PE) is a pregnancy‐specific syndrome of human pregnancy associated with poor trophoblast invasion, which attributed to 63 000 maternal and 500 000 infant deaths annually worldwide. The incidence of PE has increased by 40% over the last several decades. Elevated miR‐125b in the placenta has been reported to be linked with the risk of PE. Our bioinformatic analysis showed that voltage‐gated potassium channel subfamily A member 1 (KCNA1) is a predicted target for miR‐125b. However, roles of miR‐125b in the pathogenesis of PE is not fully explored. Here we test the hypothesis that miR‐125b is involved in the development of PE by targeting KCNA1 in human trophoblast cells. We found that expression of miR‐125b was upregulated on first trimester in patients who later developed preeclampsia(p=0.0009<0.01), while KCNA1 levels were significantly decreased and negatively correlated with miR‐125b levels in the PE placentas (r 2 =0.6099, p<0.01). We validated that KCNA1 is a direct target of miR‐125b using luciferase assay and western blotting(p<0.05). We then conducted transwell invasion assay and found that miR‐125b significantly inhibited trophoblast cell invasion by 58.67±3.48% (compared to mock, p<0.05), knockout of KCNA1 significantly attenuated the invasion‐inhibitory effect of miR‐125b (p<0.05) while overexpression of KCNA1 reversed the effect of miR‐125b (p<0.05). In conclusion, these data suggest that elevated miR‐125b impaired trophoblast invasion via directly targeting KCNA1 in the pathology of PE. The findings highlight the function of KCNA1 in human placental cells and provide new insight of how miR‐125b is involved in the pathogenesis of preeclampsia. Support or Funding Information This research was supported by the National Natural Science Foundation of China (81601318) and Shandong Province Health and Medical Science and Technology Program (2016WS0668), Weifang Medical University (No. 2017BSQD11).