Presentation Authors: Cheng Liu*, Beijing, China, People's Republic of, Luchao Li, Jinan, China, People's Republic of, Lulin Ma, Beijing, China, People's Republic of
Introduction: SMYD3, a histone H3K4 protein lysine methyltransferase , has a key role in activating of many oncogenes transcription in a variety of cancers. The carcinogenic mechanism of SMYD3 is rarely studied in bladder cancer(BCa). Here, we investigated the role of SMYD3 in regulatingautophagy and the anti-tumor effect by inhibiting SMYD3 in BCa cells.
Methods: Oncomine database and tissue microarray were used to investigate the expression of SMYD3 in clinical BCa specimens. Small interfering RNA (siRNA) was used to knockdown SMYD3 expression. We studied the relationship between autophagic flux and apoptosis using confocal microscopy, flow cytometry, western blot and cck-8 assay. Western blot assay and confocal microscopy were used to investigate SMYD3 regulated autophagy. The xenograft transplantation, animal imaging technology, immumohistochemistry(IHC) were used to test the anti-tumor effect of targeting SMYD3 In vivo.
Results: Oncomine database and TMA results showed a significant correlation between upregulated SMYD3 expression and poor overall survival. For BCa patients, SMYD3 was positively corelated with gender (p=0.018), T stage (p=0. 029) and tumor grade (p=0. 001). SMYD3 could inhibit protective autophagy by activating mTOR signaling pathway in BCa cells, and this kind of autophagy had balance relationship with apoptosis which was induced by autophagy inhibitor 3-methyladenine(3-MA). The combined administration of SMYD3 inhibitor EPZ031686 and 3-MA could inhibit mTOR signaling pathway synergically and show a dramatic anti-tumor effect.
Conclusions: SMYD3 has a potential to be a biomarker of invasive bladder cancer. Combined inhibition of SMYD3 and autophagy might be a treatment strategy for bladder cancer.