Project description:SATB1 is an important T-cell specific chromatin organizer in cutaneous T cell lymphoma, while its expression and function in Mycosis fungoides (MF) remain ambiguous. RNA-sequencing was conducted to investigate the genes regulated by SATB1 in MF-derived MJ cells by RNA-sequencing after SATB1-knockdown. With the criteria of P<0.05 and |fold change|>1.3, there were 988 genes upregulated and 1373 genes downregulated in SATB1-silencing MJ cells and further subjected to KEGG analysis. SATB1 silencing in MJ cells showed that SATB1 upregulated genes involved in eosinophil recruitment, including STAT3 and IL13, and downregulated genes in cell cycle progression.
Project description:Shock waves are widely used to treat various diseases and have numerous medical applications. In particular, extracorporeal shock waves (ESV) can substantially inhibit tumour growth. However, the therapeutic efficacy of ESV in colorectal cancer and its underlying mechanisms are not well understood. To address this gap in our knowledge, colorectal cancer cell lines HT29 and SW620 were used to generate xenograft mouse models and examined the therapeutic effects of a stepwise increase in ESV energy on tumour growth. In vivo, 60 mJ ESV significantly delayed xenograft growth compared with 120 and 240 mJ ESV, with no impact on body weight or hepatic and renal function. Transcriptome analysis revealed that 60 mJ ESV suppressed colorectal cancer cell proliferation and induced apoptosis and ferroptosis; these findings were further confirmed by immunohistochemical staining and western blotting. The in vitro study showed that ESV mechanistically suppressed cell proliferation and induced apoptosis and ferroptosis by activating the p53 signaling pathway. In conclusion, 60 mJ ESV substantially inhibited colorectal cancer growth by activating p53 pathway-related proliferation inhibition and cell death. These findings indicate that ESV therapy is a promising therapeutic strategy for colorectal cancer.
Project description:An essential step in active host cell invasion by the obligate intracellular apicomplexan parasites is the formation of a moving junction (MJ), which joins both plasma membranes and connects the underlying host cortical cytoskeleton with the parasite actomyosin system. Invading Toxoplasma gondii secrete RON complex proteins from rhoptry organelles into the host cell which provide the MJ components on the cytoplasmic side of the host cell membrane. We investigated the role of an essential organelle-resident RON13 kinase and implicated in phosphorylation of rhoptry content. Structural biology and biochemistry demonstrated that RON13 is an atypical kinase inserted N-terminally in the organelle membrane and processed by the aspartyl protease 3. In the absence of RON13 function rhoptry discharge is unaffected but parasites fail to invade cells in vitro and become avirulent in a mouse model. Comparative phosphoproteomics revealed RON13-dependent phosphorylation of secreted RONs involved in anchoring the MJ in the host cell cytoskeleton.