Recurrent implantation failure (RIF) is an intrigue condition during in vitro fertilization (IVF) cycles or intracytoplasmic sperm injection (ICSI) treatments. The purpose of this retrospective study is to explore the value of next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) of trophectoderm biopsy in the clinical outcomes for RIF patients with advanced age. A total of 265 RIF patients, who underwent 346 oocyte retrieval cycles and 250 PGT-A cycles, were classified as two groups according to the female age, including < 38 and ≥ 38 years old groups. The two groups were statistically comparable in baseline characteristics. The component of aneuploid embryos was significantly higher in advanced age group than in younger age group (68.9 vs 39.9%, P < 0.001). But there were no statistically significant differences in pregnancy rate (43.5 vs 64.7%), clinical pregnancy rate (39.1 vs 48.0%), implantation rate (39.1 vs 51.0%), and miscarriage rate (4.3 vs 7.8%) per embryo transfer (ET) between the two groups. Results suggest that the embryo-related factor plays a crucial role in RIF. Maternal age does not influence the implantation potential of euploid blastocysts. The NGS-based PGT-A involving trophectoderm biopsy is valuable for RIF patients of advanced age by improving their clinical outcomes. In conclusion, the NGS-based PGT-A involving trophectoderm biopsy may represent a valuable supplement to the current RIF management. Nonetheless, these findings should be further validated in a well-designed randomized controlled trial.
Dysregulation of microRNAs serves a crucial role in the chemosensitivity to cisplatin (DDP) in ovarian cancer (OVC). The abnormal expression of microRNA (miR)-654-3p has been reported in several types of human cancer. However, the association between miR-654-3p and cisplatin resistance in human OVC remains unclear. The present study aimed to investigate the role and mechanism of miR-654-3p in DDP resistance in OVC. The results demonstrated that miR-654-3p was significantly downregulated in ovarian cancer tissues and cells, as well as DDP-resistant IGROV-1/DDP cells, compared with adjacent non-tumoral tissue and IOSE386 cells. Overexpression of miR-654-3p significantly suppressed the proliferation and migration of ovarian cancer cells and increased the sensitivity of IGROV-1/DDP cells to DDP. Luciferase reporter assay demonstrated that quinolinate phosphoribosyl transferase (QPRT) was a target of miR-654-3p; overexpression of miR-654-3p inhibited QPRT expression by binding to the 3'-untranslated region of QPRT. In addition, inhibition of miR-654-3p reversed the suppressive effects of QPRT-targeting short interfering RNA on the proliferation and chemoresistance of ovarian cancer cells. Therefore, the results of the present study revealed a previously unrecognized regulatory mechanism that miR-654-3p enhances DDP sensitivity of OVC cells by downregulating QPRT expression; in addition, the present study highlighted the therapeutic implications of miR-654-3p upregulation in OVC.
O-GlcNAcylation is a dynamic and reversible post-translational modification associated with the regulation of multiple cellular functions. The addition and removal of O-Linked β-N-acetylglucosamine (O-GlcNAc) on target proteins is catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. Accumulating evidence suggests that O-GlcNAcylation is associated with the malignancy of several types of human cancer. To investigate the effect of O-GlcNAcylation on ovarian cancer phenotypes, global O-GlcNAc levels were decreased by OGT silencing through RNA interference and increased by inhibiting OGA activity with Thiamet-G. Transwell assay results demonstrated that OGT silencing inhibited the migration and invasion of SKOV3 and 59M ovarian cells in vitro, while Thiamet-G treatment promoted migration and invasion. Furthermore, a pull-down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho-associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. In addition, RhoA silencing via RNA interference and inhibition of ROCK activity with Y-27632 prevented Thiamet-G-induced increases in cell migration and invasion. These data suggest that O-GlcNAcylation augments the motility of ovarian cancer cells via the RhoA/ROCK/MLC signaling pathway. Therefore, O-GlcNAcylation may be a potential target for the diagnosis and treatment of ovarian cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.