Loss of Fat Mass and Obesity Associated Gene (FTO) Decreases Proliferation and Invasion in Renal Cell Carcinoma Cell-line by Upregulation of NF-kappa B signaling pathway
Sources of Funding: none
Introduction
FTO was the first GWAS identified gene which was associated with obesity, considering the interaction between obesity and renal cell carcinoma(RCC), the biological role of FTO in RCC is of great interest.
Methods
We examined the expression of the FTO gene in RCC cell lines and the effect of FTO on cell proliferation and invasion in RCC A498 and 786-O cells. Microarray processing and analysis was used to explore novel pathways involved in FTO tumorigenesis.
Results
TO was expressed at high levels in A498 cells and low levels in 786-O cells. Lentivirus-mediated FTO knockdown in RCC A498 cells caused cell-cycle increase in the G1/S phase and dramatically inhibited proliferation and invasion in culture. By contrast, over-expression of FTO in 786-O cells increased proliferation and invasion. Pathway gene chip analysis revealed that FTO knockdown resulted in the NF-kappa B signaling pathway activation. IL-1R, TLR4, BIRC2, RIG-I were significantly upregulated after FTO knockdown.
Conclusions
These findings demonstrate that FTO may alter proliferation, invasion and cell cycle of renal cell carcinoma cell lines through the NF-kappa B signaling pathway.
Funding
none
JunLong Wu
HaiLiang Zhang
GuoHai Shi
Yao Zhu
DingWei Ye