Long non-coding RNA TLR8-AS1 induces preeclampsia through increasing TLR8/STAT1 axis

Objective:Our current study tried to assay the role of long noncoding RNAs (lncRNAs) TLR8-AS1 in regulating preeclampsia.Methods:TLR8-AS1 expression was examined in the clinical placental tissues of preeclampsia patients and the trophoblast cells induced by lipopolysaccharide (LPS). Then, different lentivirus was infected into trophoblast cells to study the role of TLR8-AS1 in cell functions. Furthermore, interactions among TLR8-AS1, signal transducer and activator of transcription 1 (STAT1) and toll-like receptor 8 (TLR8) were determined. A rat model of preeclampsia induced by N(omega)-nitro-L-arginine methyl ester was developed to validate the in-vitro findings.Results:High expression of TLR8-AS1 was detected in placental tissues of preeclampsia patients and LPS-induced trophoblast cells. In addition, overexpression of TLR8-AS1 arrested the proliferation, migration and invasion of trophoblast cells, which was related to the upregulation of TLR8 expression. Mechanistically, TLR8-AS1 recruited STAT1 to bind to the TLR8 promoter region, and thus promoted the transcription of TLR8. Meanwhile, overexpression of TLR8-AS1 was shown to aggravate preeclampsia by elevating TLR8 in vivo.Conclusion:Our study confirmed that TLR8-AS1 aggravated the progression of preeclampsia through increasing the expression of STAT1 and TLR8.

Automated summary

Objective: Our study aimed to investigate the role of long noncoding RNA (lncRNA) TLR8-AS1 in regulating preeclampsia. Methods: TLR8-AS1 expression was examined in clinical placental tissues of preeclampsia patients and LPS-induced trophoblast cells. The functional role of TLR8-AS1 was studied by infecting different lentivirus into trophoblast cells. Interactions among TLR8-AS1, STAT1 and TLR8 were also determined. Furthermore, a rat model of preeclampsia was developed for in vivo validation of the in-vitro findings. Results: High expression of TLR8-AS1 was detected in placental tissues of preeclampsia patients and LPS-induced trophoblast cells. Overexpression of TLR8-AS1 inhibited the proliferation, migration and invasion of trophoblast cells through upregulation of TLR8 expression. Mechanistically, TLR8-AS1 recruited STAT1 to bind to the TLR8 promoter region, thereby promoting TLR8 transcription. Overexpression of TLR8-AS1 in vivo aggravated preeclampsia by elevating TLR8 expression. Conclusion: Our study confirmed that TLR8-AS1 aggravates the progression of preeclampsia by increasing the expression of STAT1 and TLR8.