Current medical science · 2025
The Regulatory Mechanism of MicroRNA-144-3p on Damage to Endometrial Epithelial Cells Exposed to Copper Ions In Vitro.
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Fan Xiao-Rong, Zhu Hou-Ze, Lei Meng-Ying, Jiang Peng-Jun, Zhou Hui, Xia Wei
Аннотация
OBJECTIVE: To investigate the differential expression of microRNA-144-3p in endometrial cells exposed to copper ions in vitro. The specific mechanism by which microRNA-144-3p is involved in Cu2+-induced damage to the human endometrial epithelial cells (HEECs) was explored.
METHODS: HEECs were cultured in copper-containing culture medium to simulate changes in the endometrium after copper intrauterine device (Cu-IUD) implantation. Reverse transcription quantitative PCR (RT-qPCR) was used to detect the differential expression of miR-144-3p in HEECs after Cu2+ treatment. MiRNAs, siRNAs and related inhibitors were used to treat HEECs. The expression levels of related downstream genes were then analyzed by RT-qPCR, Western blotting and immunofluorescence to explore the specific mechanism involved.
RESULTS: MiR-144-3p was significantly upregulated in the Cu2+-treated HEECs. The expression of P-NF-κB, MMP9, TGF-β3 and P-SMAD3 was significantly decreased in HEECs treated with 10 μg/mL Cu2+. MiR-144-3p regulated the expression of metallothionein 1A (MT1A) and thrombospondin-1 (THBS-1) in Cu2+-treated HEECs. The expression of P-NF-κB can be regulated by MT1A, and an inhibitor of P-NF-κB can significantly reduce the expression of MMP9 in Cu2+-treated HEECs. The expression of TGF-β3 can be regulated by THBS-1, and a TGF-β3 inhibitor can significantly reduce the expression of SMAD3 in Cu2+-treated HEECs. The proliferative capacity of HEECs treated with MMP9 or SMAD3 inhibitors was significantly reduced.
CONCLUSIONS: The increased Cu2+ concentration led to the upregulation of miR-144-3p, further reducing the expression levels of its target genes (MT1A and THBS-1), which in turn downregulated the expression of NF-κB, MMP9, TGF-β3 and SMAD3, ultimately leading to increased endometrial cell damage and decreased cell proliferation.
METHODS: HEECs were cultured in copper-containing culture medium to simulate changes in the endometrium after copper intrauterine device (Cu-IUD) implantation. Reverse transcription quantitative PCR (RT-qPCR) was used to detect the differential expression of miR-144-3p in HEECs after Cu2+ treatment. MiRNAs, siRNAs and related inhibitors were used to treat HEECs. The expression levels of related downstream genes were then analyzed by RT-qPCR, Western blotting and immunofluorescence to explore the specific mechanism involved.
RESULTS: MiR-144-3p was significantly upregulated in the Cu2+-treated HEECs. The expression of P-NF-κB, MMP9, TGF-β3 and P-SMAD3 was significantly decreased in HEECs treated with 10 μg/mL Cu2+. MiR-144-3p regulated the expression of metallothionein 1A (MT1A) and thrombospondin-1 (THBS-1) in Cu2+-treated HEECs. The expression of P-NF-κB can be regulated by MT1A, and an inhibitor of P-NF-κB can significantly reduce the expression of MMP9 in Cu2+-treated HEECs. The expression of TGF-β3 can be regulated by THBS-1, and a TGF-β3 inhibitor can significantly reduce the expression of SMAD3 in Cu2+-treated HEECs. The proliferative capacity of HEECs treated with MMP9 or SMAD3 inhibitors was significantly reduced.
CONCLUSIONS: The increased Cu2+ concentration led to the upregulation of miR-144-3p, further reducing the expression levels of its target genes (MT1A and THBS-1), which in turn downregulated the expression of NF-κB, MMP9, TGF-β3 and SMAD3, ultimately leading to increased endometrial cell damage and decreased cell proliferation.