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ST8SIA1 inhibits the proliferation,migration and invasion of bladder cancer cells by blocking the JAK/STAT signaling pathway
Authors:Shengjin Yu  Shidan Wang  Xiaoxin Sun  Yinshuang Wu  Jun Zhao  Junqiang Liu  Deyong Yang  Yu Jiang
Affiliation:1.Institute of Molecular Medicine, Medical College of Eastern Liaoning University, Dandong, Liaoning 118000, P.R. China;2.Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian, Liaoning 116044, P.R. China;3.College of Integrative Medicine, Dalian Medical University, Dalian, Liaoning 116044, P.R. China;4.Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
Abstract:Bladder cancer (BLCA) is the most common malignant tumor of the urinary system, with distant metastasis of the tumor being the main cause of death. The identification of an effective biomarker may provide a novel direction for BLCA diagnosis and treatment. The aim of the present study was to screen the BLCA-related genes involved in sialyl transferase (ST) dysregulation and to investigate the functional mechanisms of α-2,8-ST1 (ST8SIA1) in BLCA cells. Data from The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis databases suggested that the mRNA expression levels of ST8SIA1 were decreased in BLCA tissues compared with normal tissues, which was also demonstrated using immunohistochemistry and western blot analysis. The expression levels of ST8SIA1 were negatively associated with the pathological grade and invasiveness of BLCA. Western blot analysis revealed that the expression levels of ST8SIA1 were lower in BLCA cell lines than in a normal urothelial cell line. CCK-8, flow cytometry, wound healing, colony formation and Transwell assays indicated that ST8SIA1 overexpression attenuated the proliferation, migration and invasion of T24 and 5637 BLCA cells. Further experiments revealed that ST8SIA1 could inhibit the phosphorylation of Janus kinase (JAK)2 and STAT3, as well as decrease the expression levels of JAK/STAT pathway-targeting signal molecules, including MMP2, proliferating cell nuclear antigen, cyclin D1 and Bcl2 in two BLCA cell lines. In conclusion, to the best of our knowledge, the present study was the first to indicate that the antitumor effect of ST8SIA1 in BLCA cells was mediated by the JAK/STAT signaling pathway, and the results provided a novel target for the diagnosis and treatment of BLCA.
Keywords:sialyl transferase, α  -2,8-ST1, bladder cancer, growth, migration, invasion, JAK/STAT
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