Abstract
Dysregulation of noncoding RNAs has been reported to have a close correlation with preeclampsia(PE)development. TCL6 was upregulated in patients with PE. In this study, we examined the impacts of TCL6 on modulating HTR-8/SVneo cells induced by LPS. LPS (100 and 200 ng/ml) was applied to induce inflammation in trophoblast cells HTR-8/SVneo. Cell viability, apoptosis, and transwell experiments were conducted. The ELISA methods were used for pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. MDA, GSH, and GPX kits were employed. Transfection was performed for expression regulation of TCL6, miR-485-5p, and TFRC in cells. Bioinformatic online tools were used to predict the targeting sites. Luciferase and RNA immunoprecipitation-qPCR were done to verify the interactions of TCL6, miR-485-5p, and TFRC. RNA expression levels were measured using RT-qPCR, and protein expression of TFRC and GPX4 was detected using a western blot. The free Fe (II) contents were measured. LPS decreased viability, invasion, and migration but enhanced apoptosis, ferroptosis, and inflammation. TCL6 expression was enhanced by LPS induction. The knockdown of TCL6 increased HTR-8/SVneo cell viability and invasion but inhibited cell apoptosis, inflammation, and ferroptosis while inhibition of miR-485-5p could reverse this through TFRC regulation. Moreover, miR-485-5p was sponged by TCL6 and bound to TFRC. TCL6 protected trophoblast cells from LPS-induced injury through the TFRC pathway.
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Funding
This work was supported by the Open Fund of Tianjin Central Hospital of Gynecology Obstetrics/Tianjin Key Laboratory of human development and reproductive regulation (Grant Numbers: 2019XH05) and the Tianjin Health Research Project (Grant Numbers: KJ20047).
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YW, SL, HC, YC: conceptualization, methodology, software. YW, SL: data curation, writing—original draft preparation, and supervision. YW, SL: visualization, investigation. SL, YC: software, validation. YW, SL, HC, YC: writing—reviewing and editing. YW and SL contributed to the paper equally as co-first authors. All authors read and approved the final manuscript.
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Wang, Y., Liu, S., Cui, H. et al. Downregulation of TCL6 protected human trophoblast cells from LPS-induced inflammation and ferroptosis. Funct Integr Genomics 23, 226 (2023). https://doi.org/10.1007/s10142-023-01148-3
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DOI: https://doi.org/10.1007/s10142-023-01148-3