Circ_0060731 mediated miR-21–5p-PDCD4/ESR1 pathway to induce apoptosis of placental trophoblasts in intrahepatic cholestasis of pregnancy

• Published in: Tissue & cell 2022-06, Vol.76, p.101771-101771, Article 101771
• Main Authors: Feng, Fan, Lei, Lei, Liao, Junqun, Huang, Xiaomei, Shao, Yong
• Format: Article
• Language: English
• Subjects: Apoptosis; Caspase-3; Cholestasis; Chromosome 5; Circ_0060731; ESR1 protein; Gallbladder diseases; Genes; Intrahepatic cholestasis of pregnancy; MiR-21–5p; Pathogenesis; Placenta; Pregnancy; Pregnancy complications; Trophoblasts
• ISSN: 0040-8166; 1532-3072
• DOI: 10.1016/j.tice.2022.101771

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy complication. However, the pathogenesis of ICP is currently unclear. We analyzed the placenta samples of 10 normal and 10 ICP pregnant women. the expressions of circ0060731, miR-21–5p, and their downstream target genes PDCD4, ESR1, and apoptotic protein cleaved-caspase3 were detected in the cell model. The expression of Circ_0060731, PDCD4, ESR1, and caspase-3 was higher in the ICP placenta tissue than in the control group, and the expression of miR-21–5p was lower in the ICP group than in the control group. In HTR8/Svneo cells treated with TCA, the expression/levels of Circ_0060731, PDCD4, ESR1, and caspase-3 were significantly higher in the ICP group than in the control group, and miR-21–5p was significantly lower in the ICP group than in the control group. Lentiviral knockdown of miR-21–5p significantly increased the expressions of its downstream genes of PDCD4 and ESR1, and also increased cell apoptosis. Overexpression of miR-21–5p significantly reduced the expression of PDCD4 and ESR1 and reduced cell apoptosis. The dual-luciferase experiment showed that both PDCD4 and ERS1 were the target genes of miR-21–5p. Circ_0060731 mediated miR-21–5p-PDCD4/ESR1 pathway could induce apoptosis of placental trophoblasts in intrahepatic cholestasis of pregnancy. •Expression of miR-21–5p was lower in placenta of intrahepatic cholestasis of pregnancy.•Expression of circ_0060731 was higher in placenta of intrahepatic cholestasis of pregnancy.•PDCD and ESR1 are target genes of miR-21–5p.•Circ0060731 may mediate placental trophoblast apoptosis by regulating miR-21–5p-PDCD4 / ESR1 pathway.