Tumor Biology

, Volume 37, Issue 12, pp 15543–15549 | Cite as

YT521 promotes metastases of endometrial cancer by differential splicing of vascular endothelial growth factor A

Original Article

Abstract

The malignancy of endometrial carcinoma (EC) largely results from its high invasive feature. The regulation of the mRNA splicing of vascular endothelial growth factor A (VEGF-A) is critical for EC-associated cancer vascularization and invasion. Recently, we have reported that poorly prognostic EC had high levels of YT521, a newly defined RNA splicing protein. However, whether YT521 may similarly regulate the splicing of VEGF-A in EC is unknown. Here, we showed that EC specimens contained significantly higher levels of YT521, compared to the adjacent non-tumor endometrial tissue. Higher levels of YT521 were detected in EC specimens with metastases. High-YT521 EC is associated with poor patient survival. In order to examine whether YT521 may regulate VEGF-A mRNA splicing in EC, we transfected an EC cell line HEC-1A with different doses of YT521 mimics. We found that YT521 dose-dependently increased the ratio of VEGF-165 vs VEGF-121 at both mRNA and protein level, suggesting that YT521 may promote VEGF-A mRNA splicing to favor a VEGF-165 isoform. Moreover, the increases in the ratio of VEGF-165 vs VEGF-121 by YT521 overexpression resulted in increases in EC cell invasion, while decreases in the ratio of VEGF-165 vs VEGF-121 by YT521 depletion resulted in decreases in EC cell invasion in a transwell cell migration assay. Further, overexpression of VEGF-165, but not overexpression of VEGF-121, increased EC cell invasiveness. Finally, a strong correlation was detected between the ratio of VEGF-165 vs VEGF-121 and the levels of YT521 in EC specimens. Together, these data suggest that YT521 may promote EC metastases by regulating mRNA splicing of VEGF-A.

Keywords

Endometrial carcinoma Vascular endothelial growth factor A YT521 mRNA splicing 

Notes

Acknowledgments

The project was supported by Grants from the National Natural Science Foundation of China (NSFC Nos. 81202045) and the Shanghai Science and Technology Committee Foundation (13ZR1432000).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Obstetrics and Gynecology, Shanghai Tenth People’s HospitalTongji UniversityShanghaiChina

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