Abstract 2060: The pseudogeneFLT1P1functions as a tumor metastasis suppressor in a preclinical model of colorectal cancer

Abstract Chromosome 3p21.3 is one of the unstable genomic loci that are frequently altered by epigenetic modifications or interstitial deletions in human solid tumors. Several genes in 3p21.3 are known to be tumor suppressors. This locus includes a non-coding gene, fms-related tyrosine kinase 1 pseudogene 1 (FLT1P1), of which the role is largely unknown. Our previous published study (Ye et al. MCR, 2015) found that FLT1P1 was transcribed primarily as an antisense that inhibits VEGFR1 protein expression through interaction with miR-520a in human colorectal cancer (CRC) cells. In this study, we showed that the expression of FLT1P1 antisense is silenced by promoter hyper-methylation in xenograft tumors. Our data further showed that the loss of the FLT1P1 antisense not only up-regulated the expression of VEGFR1 and other genes relating to tumor angiogenesis, but also induced the EMT phenotype in tumor cells. Moreover, the FLT1P1 silenced cells demonstrated an increase in the number of metastasis to the liver following spleen injection in a mouse model. These observations suggest that the transcribed FLT1P1 antisense is a tumor metastasis suppressor. Our finding warrants further investigation of the genetic and epigenetic alterations of FLT1P1 and their impact on metastasis of CRC cells. Citation Format: Xiangcang Ye, Fan Fan, Rajat Bhattacharya, Delphine R. Boulbes, Rui Wang, Ling Xia, Lee M. Ellis. The pseudogene FLT1P1 functions as a tumor metastasis suppressor in a preclinical model of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2060.