Palmitate acid promotes gastric cancer metastasis via FABP5/SP1/UCA1 pathway

棕榈酸通过 FABP5/SP1/UCA1 通路促进胃癌转移

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作者:Jiaomeng Pan #, Qingqiang Dai #, Tianqi Zhang, Chen Li

Background

Gastric cancer (GC) has a clear predilection for metastasis toward omentum which is primarily composed of adipose tissue, combine with our previous research that long non-coding RNA Urothelial cancer associated 1 (UCA1) could promote the peritoneal metastasis of GC, we put forward the hypothesis that fatty acids (FAs) might contribute to these phenomena and a connection between FAs and UCA1 might exist.

Conclusions

Our research revealed the potential tumor-promoting effect of FA transport protein FABP5. We also established a connection between non-coding RNA and FA metabolism, treatment targeted either to patients' diets or FABP5 might improve the prognosis of GC patients.

Methods

TCGA database was applied to investigate the expression levels of UCA1 in GC tissues and normal gastric tissues and its correlation with GC patients' survival. Transfection of siRNA was utilized to knockdown cellular levels of FA-binding protein 5 (FABP5), SP1, UCA1. Migration assay and invasion assay were performed to assess the biological effects of palmitate acid (PA), FABP5, SP1 and UCA1 on GC metastasis. The underlying mechanism was investigated via western blot, immunofluorescence (IF), semi-quantitative RT-PCR (sqRT-PCR) and quantitative RT-PCR (qRT-PCR) analysis.

Results

Here we demonstrated that PA could promote the nuclear transport of FABP5, which then increased the nuclear protein levels of SP1. Consequently, GC cellular expression levels of UCA1 were increased which promoted the metastatic properties of GC. Besides, the cellular levels of UCA1 in GC tumor tissues were significantly higher than that in normal tissues. Its levels in GC tumor tissues also negatively correlated with the prognosis of GC patients using TCGA database. Conclusions: Our research revealed the potential tumor-promoting effect of FA transport protein FABP5. We also established a connection between non-coding RNA and FA metabolism, treatment targeted either to patients' diets or FABP5 might improve the prognosis of GC patients.

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