Reversal of H2O2-induced cell death by knockdown of HOTAIR in HTR-8/SVneo cells by mediation of miR-106b-5p/ACSL4 axis

Abstract

Preeclampsia is a serious threat to the health of pregnant women. Injury of trophoblasts could contribute to the progression of preeclampsia, and H₂O₂ was able to induce apoptosis in trophoblasts. LncRNAs have been reported to be involved in the progression of preeclampsia. Additionally, lncRNA HOTAIR is upregulated in patients with preeclampsia. However, the function of HOTAIR in H₂O₂-treated trophoblasts remains unclear. To explore the function of HOTAIR in preeclampsia, HTR-8/SVneo cells were stimulated with H₂O₂. RT-qPCR was performed to measure HOTAIR expression in HTR-8/SVneo cells. The apoptosis of HTR-8/SVneo cells was measured using TUNEL staining. The mitochondrial membrane potential was measured using JC-1 staining. Western blotting was performed to detect the expression of ACSL4, GPX4, and FTH1 in HTR-8/SVneo cells. The level of HOTAIR in HTR-8/SVneo cells was upregulated by H₂O₂. In addition, H₂O₂ notably inhibited the proliferation of HTR-8/SVneo cells, whereas knockdown of HOTAIR reversed this phenomenon. The mitochondrial membrane potential in HTR-8/SVneo cells was significantly inhibited by H₂O₂ and partially abolished by HOTAIR silencing. Moreover, HOTAIR could bind to miR-106b-5p; ACSL4 was identified as the downstream target of miR-106b-5p. Furthermore, HOTAIR knockdown reversed H₂O₂-induced ferroptosis in HTR-8/SVneo cells by regulating miR-106b-5p/ACSL4. Collectively, the knockdown of HOTAIR reversed H₂O₂-induced ferroptosis in HTR-8/SVneo cells by mediating miR-106b-5p/ACSL4. Thus, HOTAIR may serve as a new therapeutic target against preeclampsia.

Keywords: ACSL4; Ferroptosis; HOTAIR; Preeclampsia; miR-106b-5p.