Placenta · 2025
Reduced level of BMI1 inhibits trophoblast proliferation and migration via the epigenetic enhancement of CSTA and TGFB2 in spontaneous abortion.
СтатьяНазвание и аннотация: Перевод в очереди
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Li Huimin, Wang Gaigai, Meng Qingxia, Zhu Rui, Liu Minjuan, Zhang Xiangyun, Wang Jiaxiong, Li Hong
Аннотация
INTRODUCTION: Spontaneous abortion is the loss of a pregnancy before the 28th week of gestation in China. The precise mechanisms leading to spontaneous abortion remain largely unclear.
METHODS: The expression of BMI1 in normal pregnancy and SA villous tissues was detected by qRT-PCR and immunofluorescence staining. Cell proliferation, migration, and apoptosis were assessed to explore the role of BMI1 in HTR-8/SVneo cells. Integrated RNA-seq and ChIP-seq analysis identified direct targets involved in the effects of BMI1 on trophoblasts.
RESULTS: Individuals with SA exhibited reduced levels of BMI1 in villous tissues. The knockdown of BMI1 inhibited the proliferation, clonogenicity, and migration of trophoblast cells but enhanced apoptosis. BMI1 overexpression induced the opposite effects. Moreover, we observed enhanced proliferation, migration, and colony formation in cells that had been treated with PTC-209 and a diverse range of NAC concentrations when compared to cells treated with PTC-209 alone. Despite the reduction of ROS, complete recovery of the cellular phenotype could not be achieved. CSTA and TGFB2 were identified as direct target molecules of BMI1. Specifically, overexpression of CSTA significantly reduced the levels of phosphorylated AKT, while overexpression of TGFB2 induced a notable increase in phosphorylated SMAD2/3 proteins. Finally, cell rescue assays demonstrated that the suppression of CSTA and TGFB2 counteracted the effects of BMI1 deficiency on trophoblasts.
DISCUSSION: The regulation of trophoblast function by BMI1, including the production of ROS in the cytoplasm and the epigenetic modifications of CSTA and TGFB2 in nuclei, could facilitate the identification of mechanisms underlying SA.
METHODS: The expression of BMI1 in normal pregnancy and SA villous tissues was detected by qRT-PCR and immunofluorescence staining. Cell proliferation, migration, and apoptosis were assessed to explore the role of BMI1 in HTR-8/SVneo cells. Integrated RNA-seq and ChIP-seq analysis identified direct targets involved in the effects of BMI1 on trophoblasts.
RESULTS: Individuals with SA exhibited reduced levels of BMI1 in villous tissues. The knockdown of BMI1 inhibited the proliferation, clonogenicity, and migration of trophoblast cells but enhanced apoptosis. BMI1 overexpression induced the opposite effects. Moreover, we observed enhanced proliferation, migration, and colony formation in cells that had been treated with PTC-209 and a diverse range of NAC concentrations when compared to cells treated with PTC-209 alone. Despite the reduction of ROS, complete recovery of the cellular phenotype could not be achieved. CSTA and TGFB2 were identified as direct target molecules of BMI1. Specifically, overexpression of CSTA significantly reduced the levels of phosphorylated AKT, while overexpression of TGFB2 induced a notable increase in phosphorylated SMAD2/3 proteins. Finally, cell rescue assays demonstrated that the suppression of CSTA and TGFB2 counteracted the effects of BMI1 deficiency on trophoblasts.
DISCUSSION: The regulation of trophoblast function by BMI1, including the production of ROS in the cytoplasm and the epigenetic modifications of CSTA and TGFB2 in nuclei, could facilitate the identification of mechanisms underlying SA.