JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2016, Vol. 54 ›› Issue (5): 12-16.doi: 10.6040/j.issn.1671-7554.0.2015.1257

Previous Articles     Next Articles

Expression of histone methyltransferase SMYD3 in prostate cancer tissues and its role in mTOR pathway

XIA Chuanyou, LI Luchao, LI Xiaofeng, YAN Keqiang, ZHANG Nianzhao, FAN Yidong, LIU Cheng   

  1. Department of Urology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Received:2015-12-08 Online:2016-05-16 Published:2016-05-16

PDF (PC)

393

Abstract: Objective To determine the expression of histone methyltransferase SMYD3 in prostate cancer tissues and to explore its role and mechanism in prostate cancer progression. Methods The expression of SMYD3 in 33 pairs of prostate cancer tissues and matched non-tumor tissues were detected with immunohistochemical staining. Prostate cancer cell line LNCaP and PC3 were transfected with siRNA and SMYD3 over-expressing vectors, respectively, to evaluate their growth. The expressions of proteins involved in mTOR pathway were evaluated with Western blotting. Results Prostate cancer had over-expressed SMYD3 compared with non-tumor normal tissues. The SMYD3 expression could be found in both nucleus and cytoplasm. SMYD3 abundance had a positive correlation with cell proliferation. The number of LNCaP cells was lower in SMYD3 siRNA group compared with the control group, and the number of PC3 cells was higher in SMYD3-PC vector group than in the control group. The depletion of the enzyme could down-regulate the expression of p-mTOR(P<0.05)and p-p70S6K(P<0.05), while the expression of p-4EBP-1(P<0.05)could be up-regulated; the trend of protein expression in mTOR pathway in PC3 was similar to that in LNCaP. Conclusion SMYD3 is over-expressed in prostate cancer tissues compared with non-tumor tissues, and SMYD3 can be expressed both in nucleus and cytoplasm. The expression of SMYD3 can activate the growth of prostate cancer cells by activating mTOR pathway.

Key words: Prostate neoplasms, MTOR pathway, SiRNA, SMYD3

CLC Number: 

  • R737.25
[1] Hamamoto R, Furukawa Y, Morita M, et al. SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells[J]. Nat Cell Biol, 2004, 6(8): 731-740.
[2] Lonergan PE, Tindall DJ. Androgen receptor signaling in prostate cancer development and progression[J]. J Carcinog, 2011, 23. doi:10.4103/1477-3163.83937.
[3] Liu C, Wang C, Wang K, et al. SMYD3 as an oncogenic driver in prostate cancer by stimulation of androgen receptor transcription[J]. J Natl Cancer Inst, 2013, 105(22): 1719-1728.
[4] Nishio K, Sakai K, Togashi Y. PI3K and mTOR pathway and molecular targeted agents[J]. Nihon Rinsho, 2015, 73(8): 1315-1322.
[5] Liu Y, Bi T, Dai W, et al. Lupeol induces apoptosis and cell cycle arrest of human osteosarcoma cells through PI3K/AKT/mTOR Pathway[J]. Technol Cancer Res Treat, 2015. pii: 1533034615609014.[Epub ahead of print]
[6] Follo MY, Manzoli L, Poli A, et al. PLC and PI3K/Akt/mTOR signalling in disease and cancer[J]. Adv Biol Regul, 2015, 57: 10-16. doi: 10.1016/j.jbior.2014.10.004. Epub 2014 Nov 26.
[7] Guo Z, Hu X, Xing Z, et al. Baicalein inhibits prostate cancer cell growth and metastasis via the caveolin-1/AKT/mTOR pathway[J]. Mol Cell Biochem, 2015, 406(1-2): 111-119.
[8] Vieira FQ, Costa-Pinheiro P, Almeida-Rios D, et al. SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3[J]. Oncotarget, 2015, 6(15): 13644-13657.
[9] Bitting RL, Armstrong AJ. Targeting the PI3K/Akt/mTOR pathway in castration-resistant prostate cancer[J]. Endocr Relat Cancer, 2013, 20(3): R83-R99.
[10] Jiang SJ, Wang S. Dual targeting of mTORC1 and mTORC2 by INK-128 potently inhibits human prostate cancer cell growth in vitro and in vivo[J]. Tumour Biol, 2015, 36(10): 8177-8184.
[11] 李刚, 闫若东, 穆中一, 等. mTOR对非激素依赖性前列腺癌的作用研究[J]. 肿瘤学杂志, 2013, 19(12): 947-953. LI Gang, YAN Ruodong, MU Zhongyi, et al. Study on the effect of mTOR on androgen-independent prostate cancer[J]. Journal of Chinese Oncology, 2013, 19(12): 947-953.
[12] Edlind MP, Hsieh AC. PI3K-AKT-mTOR signaling in prostate cancer progression and androgen deprivation therapy resistance[J]. Asian J Androl, 2014, 16(3): 378-386.
[13] Park H, Kim Y, Sul JW, et al. Synergistic anticancer efficacy of MEK inhibition and dual PI3K/mTOR inhibition in castration-resistant prostate cancer[J]. Prostate, 2015, 75(15): 1747-1759.
[14] Ali AK, Nandagopal N, Lee SH. IL-15-PI3K-AKT-mTOR: a critical pathway in the life journey of natural killer cells[J]. Front Immunol, 2015, 6: 355. doi: 10.3389/fimmu.2015.00355. eCollection 2015.
[15] Guertin DA, Sabatini DM. Defining the role of mTOR in cancer[J]. Cancer Cell, 2007, 12(1):9-22.
[16] Yamamoto K, Ishida T, Nakano K, et al. SMYD3 interacts with HTLV-1 Tax and regulates subcellular localization of Tax[J]. Cancer Sci, 2011, 102(1): 260-266.
[17] Hayashi M, Deng L, Chen M, et al. Interaction of the hepatitis B virus X protein with the lysine methyltransferase SET and MYND domain-containing 3 induces activator protein 1 activation[J]. Microbiol Immunol, 2016, 60(1): 17-25.
[1] ZHANG Shi-Bao, LIU Qing-Yong, RUAN Xi-Yun, CHEN Jie, ZHANG Jian-Jun, LI Zong-Wu, YANG Guang-Xiao, WANG Quan-Ying. onstruction and identification of the expression vector of
NT4-SAC-HA2-TAT fusion gene [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 15-19.
[2] CHENG Xiangyu, XING Rui, XING Zhaoquan, GUO Zhaoxin, GUO Xiaoyu, SU Jing, MENG Liwei, LIU Zhaoxu. Effects of nitidine chloride on the proliferation and apoptosis of prostate cancer PC-3 cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(9): 13-18.
[3] ZHANG Rongjun, HAN Bo, GAO Ling, ZHU Mei, DING Guoyu, LIANG Yan. Effects of CD40 knockdown by siRNA on rats with experimental autoimmune myocarditis and IL-22 expression [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(5): 36-40.
[4] JIANG Huiyu, WANG Lin, PAN Jihong. Effects of PCSK6 silence by siRNA on FLS in CIA [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(12): 20-26.
[5] DING Ling1,2, GONG Huiping1, DU Yimeng1, WANG Xin1, ZHANG Yan3, WANG Xuping2, LU Qinghua1. Effect of SIRT3 siRNA on ICAM-1 and E-selectin expressions in HAEC stimulated by ox-LDL [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(4): 43-48.
[6] LI Yan, WEI Wei, LV Shuqing, TIAN Yongjie. Effects of PARP-1 on angiogenesis of ovarian cancer [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(4): 97-101.
[7] WANG Jie-zhong1, HAN Bo1, GAO Ling2, YANG Wen-wei1, LIU Feng-qin1, Lv-Jian-li1, Zhao Li-jian1. Effect of CD40siRNA on CD4+CD25+ regulatory T cells in rats with experimental autoimmune myocarditis [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(1): 1-4.
[8] LIU Hong-li, ZHANG You-zhong, Lv Chang-shuai, DING Bai-juan, WANG Jie. Effect of nucleolin down-regulation on biological behaviors of HeLa cells in human cervical carcinoma [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(11): 46-50.
[9] LIANG Ting-ting， ZHANG Ping， MA De-mei， ZHU Lin. Effect on apoptosis mediated by TRAIL against Caski cells of HPV16-E5-targeted siRNA [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(10): 24-28.
[10] HAN Bo1,3, YANG Xiao-qing1, ZHANG Jing2, LIU Wen-jun3, LIU Long3. Role of SPINK1 in prostate cancer: advances in experimental and
translational research [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(8): 40-.
[11] ZENG Ping, WANG Ting. Bayesian false discovery rate [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(3): 120-.
[12] XIAO Pan1, ZHANG Huai-qiang1, CUI Ya-zhou2, ZHAO Sheng-tian1, MA Tian-jia1, ZHOU Chun-wen1. A proteomics study of docetaxel-induced apoptosis in
prostate cancer PC3 cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(10): 77-.
[13] LI Wei1，LIN Hongyi1，LIU Xianxi2，WANG Wei2. Construction and identification of a prostatic androgen-independent promotermediated ODC and AdoMetDC antisense RNA-expressing adenovirus [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(6): 36-40.
[14] . Evaluation of androgendependent and androgenindependent 
proteome in LNCaP cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(9): 62-65.
[15] ZHANG Shi-Bao, LIU Qing-Yong, RUAN Xi-Yun, CHEN Jie, ZHANG Jian-Jun, LI Zong-Wu, YANG Guang-Xiao, WANG Quan-Ying. onstruction and identification of the expression vector ofNT4-SAC-HA2-TAT fusion gene [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(6): 15-19.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd