The Role Of Histone Methyltransferase SMYD3 In MTOR Pathway In Prostate Cancer

BackgroundSMYD3 is a newly found histone methyltransferase, it has been shown that SMYD3 can be highly expressed in a variety of malignant tumors, such as liver cancer, breast cancer, colon cancer, etc. As a histone methyltransferase, SMYD3 combines with repeated sequences (CCCTCC) in nueleus in cells, then activate the downstream target gene promoter to participate in a variety of biological activities. MTOR belongs to serine/threonine protein kinase family, studies have found that PI3K-AKT-mTOR signaling pathways regulating anomaly is closely related to the occurrence of some tumors, such as in breast cancer, esophageal cancer, lung cancer and other malignant tumors. And also the abnormal activation of the pathway can be found in prostate cancer. Research has shown that SMYD3 plays an important role in prostate cancer, and mainly through the activation of androgen receptor, however, our study found that in addition to the androgen-receptor pathway, there are other potential ways participating in the development of prostate cancer. We found previously that SMYD3 was involved in the potential activation of mTOR pathway through the whole transcriptome chip technology, there has not be relevant research.ObjectiveTo determine the SMYD3 expression level in prostate tissue and its impact on the growth of prostate cancer cells lines, to explore its possible mechanism.MethodsSearching in the literature and SMYD3 may influence mechanism for prostate cancer.To make the collection of prostate cancer tissue samples and the corresponding none-tumor tissues after surgery in patients with prostate cancers, using immunohistochemical technique to detect the expression level of SMYD3. To culture the two different prostate cell lines, androgen-dependent prostate cancer (LNCaP cell line) and androgen-independent prostate cancer (PC3 cell line) respectively.To do the transfection of SMYD3-siRNA and SMYD3 expression plasmid which can up-regulate the SMYD3 expression. Detecting the growth situation of PC3 cells and LNCaP cells lines, and detecting the expression of SMYD 3 and mTOR pathway proteins through western blotting.Results1. Prostate cancer tumor tissues have a high expression of SMYD3 compared with non-tumor tissues and SMYD3 expression can be found both in the cell nucleus and cytoplasm.2.LNCaP cell line has a high expression level of SMYD3,SMYD3 expression can be down-regulated after being transfected with specific SMYD3-siRNA, the growth of LNCaP cell lines were significantly suppressed, PC3 cell line has a relatively lower level of SMYD3 expression. After transfection of SMYD3 expression plasmid, the growth of PC3 cell lines was enhanced.3. The abnormal activation of mTOR pathway plays an important role in prostate cancer cells, but there is no report about SMYD3 effect in mTOR pathway. In LNCaP cell line, after being transfected with SMYD3-siRNA, the SMYD3 expression is significantly reduced, the expression of mTOR pathway is restrained. In PC3 cell line, after the transfection of SMYD3-expression plasmid, SMYD3 expression is highly enhanced, and the expression of mTOR pathway was up-regulated, the study suggests that SMYD3 can be involved in the mTOR pathway through catalytic phosphorylation.ConclusionsProstate cancer tissues have a higher expression of SMYD3 compared with non-tumor tissues. MTOR pathway can be activated by SMYD3 to regulate the growth of prostate cancer cells.