| Summary: | 碩士 === 國立中山大學 === 生物醫學研究所 === 106 === Our study explored the function and regulatory mechanisms of STMN3 which is the microtubule-destabilizing phosphoprotein in the bladder cancer. Our results showed that stable transfection of the pSTMN3-HaloTag plasmid upregulates while knockdown of the STMN3 gene suppresses STMN3 mRNA and STMN3 protein levels in J82 and BFTC905 cells, respectively. Exogenous STMN3 expression induces, while knockdown suppresses cell proliferation and alters the protein expression levels of several cell cycle regulators. Mutations on serine 50, 65 or 73 of the STMN3 protein decreases cell proliferation and colony formation/anchorage-independent cell growth in J82 cells. Inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MAP2K) stabilize acetylated-tubulin. Mutagenesis on several potential phosphorylated serines in the STMN3 protein slightly decrease actin polymerization in J82 cells. Taken together, our data indicated that STMN3 functions as an oncogene in bladder cancer, and regulated by PI3K and MEK/ERK signaling pathways, also interfered microtubule and actin polymerization stability.
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