Background
Heat shock protein 60 (HSP60) is essential for the folding and assembly of newly imported proteins to the mitochondria. HSP60 is overexpressed in most types of cancer, but its association with ovarian cancer is still in dispute. SKOV3 and OVCAR3 were used as experimental models after comparing the expression level of mitochondrial HSP60 in a normal human ovarian epithelial cell line and four ovarian cancer cell lines.
Results
Low HSPD1 (Heat Shock Protein Family D (HSP60) Member 1) expression was associated with unfavorable prognosis in ovarian cancer patients. Knockdown of HSPD1 significantly promoted the proliferation and migration of ovarian cancer cells. The differentially expressed proteins after HSPD1 knockdown were enriched in the lipoic acid (LA) biosynthesis and metabolism pathway, in which mitochondrial 3-oxoacyl-ACP synthase (OXSM) was the most downregulated protein and responsible for lipoic acid synthesis. HSP60 interacted with OXSM and overexpression of OXSM or LA treatment could reverse proliferation promotion mediated by HSPD1 knockdown.
Conclusions
HSP60 interacted with OXSM and maintained its stability. Knockdown of HSPD1 could promote the proliferation and migration of SKOV3 and OVCAR3 via lowering the protein level of OXSM and LA synthesis.
The remodeling of uterine spiral arteries is a complex process requiring the dynamic action of various cell types. During early pregnancy, extravillous trophoblast cells (EVT) differentiate and invade the vascular wall, replacing the vascular smooth muscle cells (VSMCs). Several in vitro studies have shown that EVT cells play an important role in promoting VSMC apoptosis, however the mechanism underlying this process is not fully understood. In this study, we demonstrated that EVT conditioned media and EVT-derived exosomes could induce VSMC apoptosis. Through data mining and experimental verification, it was demonstrated that the EVT exosome miR-143-3p induced VSMC apoptosis in both VSMCs and a chorionic plate artery (CPA) model. Furthermore, FAS ligand was also expressed on the EVT-exosomes and may play a coordinated role in apoptosis induction. These data clearly demonstrated that VSMC apoptosis is mediated by EVT-derived exosomes and their cargo of miR-143-3p as well as their cell surface presentation of FASL. This finding increases our understanding of the molecular mechanisms underlying the regulation of VSMC apoptosis during spiral artery remodeling.
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