LMSSitesePortfolio註冊登入
P-15 CPEB1 functions as a tumor suppressor in neuroblastoma cells through inhibition on proliferation and invasion
by 陳輔卿, 2015-09-14 19:35, 人氣(742)
P-15

CPEB1 functions as a tumor suppressor in neuroblastoma cells through inhibition on proliferation and invasion

 

Ya-Hui Tsai1,2 , Yun Chen1,2

1Department of Surgery, Far Eastern Memorial Hospital, Pan-Chiao, New Taipei City, Taiwan
2Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li, Taoyuan, Taiwan

 

Background/Purpose:

The CPEB (cytoplasmic polyadenylation element binding) proteins control the elongation of poly(A)-tail during RNA translation. CPEB1 is correlated with decreased tumor growth in various cancers. However, the role of CPEB1 in neuroblastomas is unclear. In this research, we aim to investigate CPEB1 in tumorigenesis of neuroblastomas.

Methods:

SH-SY5Y and BE(2)-M17 were used in this study. The endogenous level of CPEB1 was analyzed by western blotting. The CPEB1-expressing plasmid was constructed for ectopic expression. The cell viability, migration, and MMP activity in control and CPEB1-over-expressing cells were compared through MTT assay, in vitro invasion assay, and gelatin zymography, respectively. The miRNAs associated with MMP expression were quantified with real-time PCR.

Results:

The endogenous level of CPEB1 was very low in both neuroblastoma cells. With CPEB1 over-expression, the neuroblastoma cells displayed massive cell deaths and loss of migration ability. Analysis of MMP activities demonstrated a significant decrease in the MMP-2 activity. The quantitative expression of miRNA species which target MMP-2 showed that CPEB1 induced the expression of miR-218 with a 3.12-fold increase. Over-expression of miR-218 alone significantly inhibited the expression of MMP-2 whereas introduction of the antagomir of miR-218 into the CPEB1 over-expressing cells could rescue the expression of MMP-2.

Conclusions:

In human neuroblastoma cells, CPEB1 functions as a tumor suppressor by inhibiting cell growth and invasion ability. The miR-218-mediated repression of MMP-2 is a novel finding in the tumor-suppressing mechanism of CPEB1.