Dataset Information

VEGFR-1 Pseudogene Expression and Regulatory Function in Human Colorectal Cancer Cells.

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.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.

SUBMITTER: Ye X

PROVIDER: S-EPMC4573265 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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VEGFR-1 Pseudogene Expression and Regulatory Function in Human Colorectal Cancer Cells.

Ye Xiangcang X Fan Fan F Bhattacharya Rajat R Bellister Seth S Boulbes Delphine R DR Wang Rui R Xia Ling L Ivan Cristina C Zheng Xiaofeng X Calin George A GA Calin George A GA Wang Jing J Lu Xiongbin X Ellis Lee M LM

Molecular cancer research : MCR 20150603 9

<h4>Unlabelled</h4>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 ...[more]

PMID: 26041938

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Project description:OBJECTIVE:Colorectal cancer (CRC) is an extremely common gastrointestinal malignancy. The present study aimed to identify microRNAs (miRNAs) and transcription factors (TFs) associated with tumor development. METHODS:Three miRNA profile datasets were integrated and analyzed to elucidate the potential key candidate miRNAs in CRC. The starBase database was used to identify the potential targets of common differentially expressed miRNAs (DEMs). Transcriptional Regulatory Element Database and Transcriptional Regulatory Relationships Unraveled by Sentence-based Text databases were used to identify cancer-related TFs and the TF-regulated target genes. Functional and pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integration Discovery (DAVID) database, and the miRNA-TF-gene networks were constructed by Cytoscape. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of genes and miRNAs. RESULTS:In total, 14 DEMs were found in CRC. By bioinformatics analysis, 5 DEMs (miR-145, miR-497, miR-30a, miR-31, and miR-20a) and 8 TFs (ELK4 (ETS-family transcription factor), myeloblastosis proto-oncogene like (MYBL)1, MYBL2, CEBPA, PPARA, PPARD, PPARG, and endothelial PAS domain protein (EPAS1)) appeared to be associated with CRC and were therefore used to construct miRNA-TF-gene networks. From the networks, we found that miR-20a might play the most important role as an miRNA in the networks. By qRT-PCR, we demonstrated that miR-20a was significantly upregulated in CRC tissues. We also performed qRT-PCR to identify the expression of miR-20a-related TFs (PPARA, PPARD, PPARG, EPAS1). Three of them, PPARA, PPARG, and EPAS1, were downregulated in CRC tissues, with statistically significant differences, while the downregulation of PPARD in CRC tissues was not significantly different. Pathway enrichment analyses indicated that the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway was the most significantly enriched pathway. Two main elements of the PI3K-Akt signaling pathway, phosphatase and tensin homolog deleted on chromosome 10 and B-cell lymphoma 2-associated agonist of cell death, were demonstrated to be downregulated in CRC. CONCLUSION:The present study identified hub miRNAs and miRNA-related TF regulatory networks in CRC, which might be potential targets for the diagnosis and treatment of CRC.

Dataset Information

VEGFR-1 Pseudogene Expression and Regulatory Function in Human Colorectal Cancer Cells.

Publications

VEGFR-1 Pseudogene Expression and Regulatory Function in Human Colorectal Cancer Cells.

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