Background/Aims: Our study aims to investigate the role, effect and mechanisms of ESRP1 (epithelial splicing regulatory protein 1) in epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer (EOC). Methods: Microarray and immunohistochemical analysis of ESRP1 expression were performed in EOC cases. The correlations between ESRP1 expression and clinical factors on EOC were assessed. Lentivirus-mediated RNA interference and EGFP vector which contains ESRP1 gene were used to down-regulate and up-regulate ESRP1 expression in human EOC cell lines. Roles of ESRP1 in cell growth, migration and invasion of EOC cells were also measured by Cell Counting Kit-8 and Transwell systems in vitro and by a nude mice intraperitoneal transplantation model in vivo. Results: By the analysis of Gene Expression Omnibus (GEO) (p<0.05) and our own microarray data (p<0.001), ESRP1 expression in EOC was significantly different from normal ovarian tissue. It was abundant in the nuclei of cancer cells and in malignant lesions. However, it was weakly expressed or negative in both normal and benign lesions. High ESRP1 expression in EOC was associated with poor clinical outcomes. Decreased ESRP1 expression significantly increased cell migration and invasion both in vivo and in vitro. Snail strongly repressed ESRP1 transcription through binding to the ESRP1 promoter in EOC cells. Furthermore, ESRP1 regulated the expression of CD44s. Down-regulated ESRP1 resulted in an isoform switching from CD44v to CD44s, which modulated epithelial-mesenchymal transition (EMT) program in EOC. Up-regulatin of ESRP1 was detected in mesenchymal to epithelial transition (MET) in vivo. Conclusions: ESRP1 regulates CD44 alternative splicing during the EMT process which plays an important role in EOC carcinogenesis. In addition, ESRP1 is associated with disease prognosis in EOC.Jie Tang, MD, Ph.D, Professor 283 Tongzipo Road, Yuelu District,
Raffinose family oligosaccharides (RFOs) accumulate under stress conditions in many plants and have been suggested to act as stress protectants. To elucidate the metabolic process of RFOs under cold stress, levels of RFOs, and related carbohydrates, the expression and activities of main metabolic enzymes and their subcellular compartments were investigated during low-temperature treatment and during the recovery period in cucumber leaves. Cold stress induced the accumulation of stachyose in vacuoles, galactinol in vacuoles and cytosol, and sucrose and raffinose in vacuoles, cytosol, and chloroplasts. After cold stress removal, levels of these sugars decreased gradually in the respective compartments. Among four galactinol synthase genes (CsGS), CsGS1 was not affected by cold stress, while the other three CsGSs were up-regulated by low temperature. RNA levels of acid-α-galactosidase (GAL) 3 and alkaline-α-galactosidase (AGA) 2 and 3, and the activities of GAL and AGA, were up-regulated after cold stress removal. GAL3 protein and GAL activity were exclusively located in vacuoles, whereas AGA2 and AGA 3 proteins were found in cytosol and chloroplasts, respectively. The results indicate that RFOs, which accumulated during cold stress in different subcellular compartments in cucumber leaves, could be catabolized in situ by different galactosidases after stress removal.
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