ABSTRACT
The circulatory system is a closed conduit system throughout the body and consists of two parts as follows: the cardiovascular system and the lymphatic system. Hematological malignancies usually grow and multiply in the circulatory system, directly or indirectly affecting its function. These malignancies include multiple myeloma, leukemia, and lymphoma. O-linked ß-N-acetylglucosamine (O-GlcNAc) transferase (OGT) regulates the function and stability of substrate proteins through O-GlcNAc modification. Abnormally expressed OGT is strongly associated with tumorigenesis, including hematological malignancies, colorectal cancer, liver cancer, breast cancer, and prostate cancer. In cells, OGT can assemble with a variety of proteins to form complexes to exercise related biological functions, such as OGT/HCF-1, OGT/TET, NSL, and then regulate glucose metabolism, gene transcription, cell proliferation, and other biological processes, thus affecting the development of hematological malignancies. This review summarizes the complexes involved in the assembly of OGT in cells and the role of related OGT complexes in hematological malignancies. Unraveling the complex network regulated by the OGT complex will facilitate a better understanding of hematologic malignancy development and progression.
ABSTRACT
BACKGROUND: Preeclampsia (PE) is a pregnancy related disease that affects about 5% of pregnancies. Death receptor 3 (DR3) expression is significantly elevated in both placental tissue and plasma of PE patients. However, whether DR3 was involved in trophoblasts in pathogenesis of PE are not well elucidated. OBJECTIVE: Our research was designed to illustrate the biological roles of DR3 in placental trophoblasts, as well as explain its relevant mechanisms. METHODS: HTR-8/SVneo cells viability, migration, invasion, and apoptosis were assessed using MTT, Transwell assay, and flow cytometry analysis, respectively. Levels of DR3, PI3K, and AKT in HTR-8/SVneo cells were analyzed via reverse transcription-quantitative polymerase chain reaction assay. Western blot analysis was utilized to assess DR3, p-PI3K, p-AKT, PI3K, and AKT protein expression. RESULTS: Upregulation of DR3 obviously inhibited HTR-8/SVneo cells viability, migration, and invasion, as well as promoted HTR-8/SVneo cells apoptosis, as opposed to the control-plasmid group. We also found that DR3-plasmid enhanced cleaved-caspase3 expression, reduced p-PI3K and p-AKT protein expression, and p-PI3K/PI3K or p-AKT/AKT ratio in HTR-8/SVneo cells. Importantly, IGF-1, a PI3K/AKT signaling pathway agonist, partially reversed the effects of DR3-plasmid on the cell viability, migration, invasion, apoptosis, and PI3K/AKT signal pathway in HTR-8/SVneo cells. CONCLUSION: DR3 was involved in PE through regulating placental trophoblast cell physiology via PI3K/AKT pathway, which might be a promising therapeutic target for PE therapy.
ABSTRACT
The putative methyltransferase Lae1 is a global regulator in Trichoderma, which modulates the expression of secondary metabolite gene clusters, possibly via chromatin remodeling. Here we aimed to explore the specific transcription and metabolites profiles regulated by Lae1 in T. atroviride 23. Comparative transcriptomics and metabolome analyses between the lae1 deletion (Mlae1) and over-expressing (Olae1) mutants were performed using RNA sequencing and QTOF-UPLC-MS techniques. In total, 1344 unique differentially expressed genes (DEGs) and 92 metabolites were identified across three strains. The significantly altered metabolic profiles revealed that the lae1 gene modulates central carbon metabolism, amino acid metabolism, secondary metabolism, and phospholipid metabolism. The effects of lae1 on phospholipid metabolism were further explored, and the findings showed that lae1 modulates the composition and function of cell membranes and other metabolic activities, including the phosphotransferase system (PTS) and biosynthesis of secondary metabolites (SM). Phospholipid metabolism is related to energy metabolism, signal transduction, and environmental adaptability of microorganisms. These data showed that Lae1 affects the primary metabolites, phospholipid, as well as the regulation of secondary metabolites in Trichoderma. This study could potentially provoke in-depth investigations of the Lae1-mediated target genes in phospholipid synthesis. The Lae1 may act as a novel target that is associated with disease defense and drug development in the future.
