Role of EZH2 in the Growth of Prostate Cancer Stem Cells Isolated from LNCaP Cells

نویسندگان

  • Kuiqing Li
  • Cheng Liu
  • Bangfen Zhou
  • Liangkuan Bi
  • Hai Huang
  • Tianxin Lin
  • Kewei Xu
چکیده

Enhancer of zeste homolog 2 (EZH2) plays a crucial role in embryonic and somatic stem cells for their proliferation and differentiation. However, the roles and underlying mechanisms of EZH2 in prostate cancer stem cells (PCSCs) remain unknown. This study aimed to investigate the effects of EZH2 on PCSCs. PCSCs were isolated from the human prostate cancer cell line LNcap by fluorescence activated cell sorting (FACS). EZH2 expression was compared between PCSCs and non-PCSCs. The association between EZH2 function and PCSC growth was investigated using siRNA-mediated knock-down of EZH2. Cell growth was investigated by MTT, cell cycle and apoptosis of PCSCs were explored by flow cytometric analysis. Finally, the upstream pathway miRNA level was determined via a luciferase reporter assay, and the downstream pathway cycle regulators were examined via reverse transcriptase-polymerase chain reaction. The results showed that LNcap cell line comprised a greater proportion of CD44+/CD133+ cells by comparison to the PC-3 cell line. EZH2 was up-regulated in PCSCs compared with non-PCSCs. Silence of EZH2 inhibited cell growth and the cell cycle and promoted the progression of apoptosis. Furthermore, EZH2 was a direct target of miR-101 in PCSCs and EZH2's mRNA levels were inversely correlated with miR-101 expression and cyclin E2 (a cell-cycle regulator) was suppressed by siEZH2. In conclusion, EZH2 is essential for PCSC growth, partly through a negative regulation by miR-101 and positively regulating cyclin E2.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Synergistic Effects of NDRG2 Overexpression and Radiotherapy on Cell Death of Human Prostate LNCaP Cells

Background: Radiation therapy is among the most conventional cancer therapeutic modalities with effective local tumor control. However, due to the development of radio-resistance, tumor recurrence and metastasis often occur following radiation therapy. In recent years, combination of radiotherapy and gene therapy has been suggested to overcome this problem. The aim of the current study was to e...

متن کامل

Doxorubicin Loaded DNA Aptamer Linked Myristilated Chitosan Nanogel for Targeted Drug Delivery to Prostate Cancer

Recently, specific attention has been paid to aptamers, short DNA or RNA, as a tool for cancer diagnosis and therapy. In the present study MCS nanogels were prepared by Myristate: chitosan at 1:9 ratio and were characterized by several techniques. A selected ssDNA aptamer(Apt) capable of detecting LNCaP cells was linked to Myristilated chitosan nanogels (Apt-MCS) by glutaraldehyde and loaded wi...

متن کامل

Study of NGEP expression in androgen sensitive prostate cancer cells: A potential target for immunotherapy

  Background: Prostate cancer is one of the leading causes of cancer deaths among men. New gene expressed in prostate (NGEP), is a prostate-specific gene expressed only in normal prostate and prostate cancer tissue. Because of its selective expression in prostate cancer cell surface, NGEP is a potential immunotherapeutic target. To target the NGEP in prostate cancer, it is essential to investig...

متن کامل

PI3K and mTOR inhibitor, NVP-BEZ235, is more toxic than X-rays in prostate cancer cells

Background: Radiotherapy and adjuvant androgen deprivation therapy have historically been the first treatment choices for prostate cancer but treatment resistance often limits the capacity to effectively manage the disease. Therefore, alternative therapeutic approaches are needed. Here, the efficacies of radiotherapy and targeting the pro-survival cell signaling components epidermal growth fact...

متن کامل

Effect of EZH2 Inhibition on Colorectal Cancer Cells: an In Vitro Study

Recently, the epigenetic modifications have been recognized as a regulator of gene expression in various cancers. EZH2 gene is one the most important component of the PRC2 complex. Overexpression of EZH2 was identified in multiple cancers that considered more attractive the EZH2 role as an oncogene. Some studies report that EZH2 contributes to various aspects of colorectal cancer (CRC). However...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 14  شماره 

صفحات  -

تاریخ انتشار 2013