A Preliminary Study Of The Histone Methyltransferase SMYD3in The Role Of Prostate Cancer Cells PC3

BackgroundProstate cancer is one of the common maligant tumors of the male urinary system.According to the statistics in2011, approximately220890new cases of PCa were diagnosed in the United States,which took the first place in all manligant tumors, and the death toll was33270cases second only to lung cancer in second place. Asian countries including China is a low area, accompanied by the rapid development of China’s economic level, the great changes of people’s lifestyle, and the gradual aging population, as well as environmental factors change, coupled with the enhancement of people’s health awareness,the incidence and detection rate of PCa has increased recent years, which makes a serious threat to the quality of life and life expectancy of China’s middle-aged men. This is worth of our attention. Currently, the pathogenesis of prostate cancer is not yet very clear. Numerous molecular studies have shown that maligant transformation of prostate cancer cells is a multi-step and multi-factor complex process, involving not only the activation of oncogenes and tumor suppressor gene inactivation, epigenetic dysregulation of a set of genes related to cell proliferation,apoptosis and differention also play an important role.Therefore, the role of epigenetics in prostate cancer is increasingly attracted the attention of scholars, which histone modification is a hot topic in the study. Histone modifications can regulate chromatin structure, gene trascription and silent,through the post-translational modifications of specific residues such as histone methylation, acetylation and phosphorylation,etc.Previous studies have shown that histone methylation plays an important role in the process of cell biology,including heterochromatin formation, transcriptional regulation, DNA methylation and X chromosome inactivation.SET and MYND domain-containing protein3(SMYD3) was first found by Hamamoto, etc. in2004, a histone H3-K4methylase, playing an improtant role in the carcinogenesis and development of many malignant tumors in humans, such as hepatocellular carcinoma, colon cancer, breast cancer and cholangiocarcinoma. The in vitro experiments also showed that SMYD3has accelerated cell proliferation, inhibit apoptosis, promote the role of tumor cell colony formation. SMYD3is able to alter the modification status of chromosomal histone methylation,and regulate the expression of a set of downstream gene through the combination of its promoter region-specific sites,,thus have an impact on cell proliferation, migration, and apoptosis. The abnormal activation of telomerase is one of the key steps of malignant transformation and uncontrolled proliferation, and play an important role in the pathogenesis of prostate cancer. Liu et al found that SMYD3directly trans-activates the human telomerase reverse transcriptase(hTERT) gene that is essential for cellular immortalization and transformation. SMYD3occupies its binding motifs on the hTERT promoter and is required for maintance of histone H3-K4trimethylation. Some scholars have found a high proportion of histone methylation in prostate cancer patients. In view of this, we hypothesized that SMYD3may also play a role in the development of prostate cancer. Our preliminary studies have shown that SMYD3up-regulated in most prostate cancer tissues, and undetectable or very weak in normal prostate tissue. At present, there is no reports of SMYD3related to prostate cancer cells..ObjectiveTo study the expression of SET and MYND domain-containing protein3(SMYD3) in prostate cancer cells PC3and explore the SMYD3gene silencing on the expression of human telomerase reverse transcriptase (hTERT) and PC3cell proliferation and apoptosis. MethodsWestern blot and RT-PCR was performed to detect the expression of SMYD3in PC3cell. The use of siRNA inhibited SMYD3expression in PC3cells,RT-PCR to observe hTERT transcription level changes, CCK-8kit to detect cell proliferation and flow cytometry dection of apoptpsis.ResultsThe expression of SMYD3in protein and mRNA levels was detected in PC3cells.After the inhibition of SMYD3gene in PC3cell,hTERT transcription level decreased notably,cell proliferation was significantly inhibited (P<0.05), FCM showed that apoptosis was significantly increased (P<0.05).ConclusionSMYD3may play an important role in the progress of prostate cancer,which is useful to our further understanding of the pathogenesis of prostate cancer.