VEGFR-1 pseudogene expression and regulatory function in human colorectal cancer cells

Xiangcang Ye, Fan Fan, Rajat Bhattacharya, Seth Bellister, Delphine R. Boulbes, Rui Wang, Ling Xia, Cristina Ivan, Xiaofeng Zheng, George A. Calin, Jing Wang, Xiongbin Lu, Lee M. Ellis

Research output: Contribution to journalArticle

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Abstract

A large number of pseudogenes have been found to be transcribed in human cancers. However, only a few pseudogenes are functionally characterized. Here, we identified a transcribed pseudogene of VEGFR1, or fms-related tyrosine kinase 1(FLT1), in human colorectal cancer cells. Interestingly, this pseudogene (designated as FLT1P1) was found to be transcribed bidirectionally and functionally modulated cognate VEGFR1 protein expression in the cells. Mechanistically, expression of FLT1P1 antisense transcript not only inhibited the VEGFR1 expression, but also inhibited non-cognate VEGF-A expression through interaction with miR-520a. Perturbation of FLT1P1 expression by RNA interference (RNAi) markedly inhibited tumor cell proliferation and xenograft tumor growth. This study identifies FLT1P1 antisense as a critical regulator of VEGFR1 and VEGF-A expression in colorectal cancer cells, and highlights its role in regulation of the pathogenesis of colorectal cancer. Implications: The VEGFR1 pseudogene, FLT1P1, is a novel and functional regulator of VEGF signaling and its targeting could be an alternative strategy to modulate its cognate/target gene expression and downstream activity in cancer.

Original languageEnglish (US)
Pages (from-to)1274-1282
Number of pages9
JournalMolecular Cancer Research
Volume13
Issue number9
DOIs
StatePublished - Sep 1 2015
Externally publishedYes

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Vascular Endothelial Growth Factor Receptor-1
Pseudogenes
Colorectal Neoplasms
Vascular Endothelial Growth Factor A
Neoplasms
RNA Interference
Heterografts
Protein-Tyrosine Kinases
Cell Proliferation
Gene Expression
Growth
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

VEGFR-1 pseudogene expression and regulatory function in human colorectal cancer cells. / Ye, Xiangcang; Fan, Fan; Bhattacharya, Rajat; Bellister, Seth; Boulbes, Delphine R.; Wang, Rui; Xia, Ling; Ivan, Cristina; Zheng, Xiaofeng; Calin, George A.; Wang, Jing; Lu, Xiongbin; Ellis, Lee M.

In: Molecular Cancer Research, Vol. 13, No. 9, 01.09.2015, p. 1274-1282.

Research output: Contribution to journalArticle

Ye, X, Fan, F, Bhattacharya, R, Bellister, S, Boulbes, DR, Wang, R, Xia, L, Ivan, C, Zheng, X, Calin, GA, Wang, J, Lu, X & Ellis, LM 2015, 'VEGFR-1 pseudogene expression and regulatory function in human colorectal cancer cells', Molecular Cancer Research, vol. 13, no. 9, pp. 1274-1282. https://doi.org/10.1158/1541-7786.MCR-15-0061
Ye, Xiangcang ; Fan, Fan ; Bhattacharya, Rajat ; Bellister, Seth ; Boulbes, Delphine R. ; Wang, Rui ; Xia, Ling ; Ivan, Cristina ; Zheng, Xiaofeng ; Calin, George A. ; Wang, Jing ; Lu, Xiongbin ; Ellis, Lee M. / VEGFR-1 pseudogene expression and regulatory function in human colorectal cancer cells. In: Molecular Cancer Research. 2015 ; Vol. 13, No. 9. pp. 1274-1282.
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