Placenta · 2023
MiR-135b-5p targets ADAM12 to suppress invasion and accelerate trophoblast apoptosis in preeclampsia.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Sun Bo, Jiang Taotao, Yong Jiayao, Peng Julan, Dong Shangkun, Gu Yanli, Ji Xinmei, Luo Liqiong, Chang Wen-Lin
Аннотация
INTRODUCTION: Preeclampsia was a serious complication often leaded to adverse pregnancy outcomes. Abnormal placental miR-135b-5p expression in preeclampsia was observed in our preliminary investigation. However, the role of miR-135b-5p in preeclampsia was unclear.
METHODS: We determined the miR-135b-5p expression pattern at the fetomaternal interface and levels in placental tissue and exosomes. MiR-135b-5p expression in the trophoblast cell line HTR8/SVneo was manipulated by transient agomir or antagomir transfection or establishment of HTR8/SVneo cell line stably overexpressing miR-135b or miR-135b-5p-sponger. Then the function of miR-135b-5p on the motility of HTR8/SVneo cells, and its effects on cell viability was determined. Finally, we confirmed the relationship between miR-135b-5p and ADAM12.
RESULTS: MiR-135b-5p exclusively expressed in the villous cytotrophoblast, and extravillous trophoblast. Significant miR-135b-5p upregulation was observed in the placenta and peripheral plasma exosomes in preeclampsia, and could be a highly sensitive molecular marker for preeclampsia. Elevated miR-135b-5p expression significantly promoted apoptosis and inhibited HTR8/SVneo cell invasion and migration. Binding of miR-135b-5p to the ADAM12 mRNA 3'-untranslated region was predicted by bioinformatics analysis and confirmed using a dual-luciferase reporter assay. High miR-135-5p levels inhibit the invasion and migration of trophoblastic cells, possibly by directly binding to the 3'-UTR of DADM12 and suppressing its translation efficiency, thereby nullifying the promotion of trophoblast invasion and migration via ADAM12.
DISCUSSION: Abnormal upregulation of miR-135b-5p may be involved in preeclampsia through triggering trophoblast apoptosis and impeding trophoblast invasion and migration by targeting ADAM12.
METHODS: We determined the miR-135b-5p expression pattern at the fetomaternal interface and levels in placental tissue and exosomes. MiR-135b-5p expression in the trophoblast cell line HTR8/SVneo was manipulated by transient agomir or antagomir transfection or establishment of HTR8/SVneo cell line stably overexpressing miR-135b or miR-135b-5p-sponger. Then the function of miR-135b-5p on the motility of HTR8/SVneo cells, and its effects on cell viability was determined. Finally, we confirmed the relationship between miR-135b-5p and ADAM12.
RESULTS: MiR-135b-5p exclusively expressed in the villous cytotrophoblast, and extravillous trophoblast. Significant miR-135b-5p upregulation was observed in the placenta and peripheral plasma exosomes in preeclampsia, and could be a highly sensitive molecular marker for preeclampsia. Elevated miR-135b-5p expression significantly promoted apoptosis and inhibited HTR8/SVneo cell invasion and migration. Binding of miR-135b-5p to the ADAM12 mRNA 3'-untranslated region was predicted by bioinformatics analysis and confirmed using a dual-luciferase reporter assay. High miR-135-5p levels inhibit the invasion and migration of trophoblastic cells, possibly by directly binding to the 3'-UTR of DADM12 and suppressing its translation efficiency, thereby nullifying the promotion of trophoblast invasion and migration via ADAM12.
DISCUSSION: Abnormal upregulation of miR-135b-5p may be involved in preeclampsia through triggering trophoblast apoptosis and impeding trophoblast invasion and migration by targeting ADAM12.