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Oncogenic Activity of Wrap53 in Human Colorectal Cancer In Vitro and in Nude Mouse Xenografts.

ABSTRACT: BACKGROUND WD40-encoding RNA antisense to p53 (Wrap53) has been implicated in cancer development. However, the role of Wrap53 remains unknown in colorectal cancer. The aim of this study was to elucidate the function of Wrap53 in colorectal cancer tumorigenesis and development. MATERIAL AND METHODS This study analyzed Wrap53 expression in colorectal cancer tissue specimens using The Cancer Genome Atlas data and tumor cell lines and assessed the effects of Wrap53 knockdown on regulation of cancer cell malignant phenotypes in vitro and in nude mouse xenografts. RESULTS Wrap53 expression was upregulated in colorectal cancer tissue specimens and cell lines. Knockdown of Wrap53 expression induced colorectal cancer cell line apoptosis and cell cycle arrest in the G1 phase, but reduced tumor cell line proliferation and invasion in vitro. Knockdown of Wrap53 in a nude mouse xenograft assay inhibited tumor cell line xenograft formation and growth. CONCLUSIONS Wrap53 is likely a potential oncogene or possesses oncogenic activity in colorectal cancer, promoting colorectal tumorigenesis. Targeting Wrap53 expression may represent a novel strategy for the control of colorectal cancer.

SUBMITTER: Zhu Y

PROVIDER: S-EPMC6131976 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Oncogenic Activity of Wrap53 in Human Colorectal Cancer In Vitro and in Nude Mouse Xenografts.

Zhu Yu Y Ding Lei L Chen Bai-Feng BF Song Jian-Gen JG Yao Ying-Shui YS

Medical science monitor : international medical journal of experimental and clinical research 20180903

BACKGROUND WD40-encoding RNA antisense to p53 (Wrap53) has been implicated in cancer development. However, the role of Wrap53 remains unknown in colorectal cancer. The aim of this study was to elucidate the function of Wrap53 in colorectal cancer tumorigenesis and development. MATERIAL AND METHODS This study analyzed Wrap53 expression in colorectal cancer tissue specimens using The Cancer Genome Atlas data and tumor cell lines and assessed the effects of Wrap53 knockdown on regulation of cancer ...[more]

PMID: 30175821

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Project description:The non-receptor tyrosine kinase SRC is frequently deregulated in human colorectal cancer (CRC), and SRC increased activity has been associated with poor clinical outcomes. In nude mice engrafted with human CRC cells, SRC over-expression favors tumor growth and is accompanied by a robust increase in tyrosine phosphorylation in tumor cells. How SRC contributes to this tumorigenic process is largely unknown. We analyzed SRC oncogenic signaling in these tumors by means of a novel quantitative proteomic analysis. This method is based on stable isotope labeling with amino acids of xenograft tumors by the addition of [(13)C(6)]-lysine into mouse food. An incorporation level greater than 88% was obtained in xenograft tumors after 30 days of the heavy lysine diet. Quantitative phosphoproteomic analysis of these tumors allowed the identification of 61 proteins that exhibited a significant increase in tyrosine phosphorylation and/or association with tyrosine phosphorylated proteins upon SRC expression. These mainly included molecules implicated in vesicular trafficking and signaling and RNA binding proteins. Most of these proteins were specific targets of SRC signaling in vivo, as they were not identified by analysis via stable isotope labeling by amino acids in cell culture (SILAC) of the same CRC cells in culture. This suggests that oncogenic signaling induced by SRC in tumors significantly differs from that induced by SRC in cell culture. We next confirmed this notion experimentally with the example of the vesicular trafficking protein and SRC substrate TOM1L1. We found that whereas TOM1L1 depletion only slightly affected SRC-induced proliferation of CRC cells in vitro, it drastically decreased tumor growth in xenografted nude mice. We thus concluded that this vesicular trafficking protein plays an important role in SRC-induced tumor growth. Overall, these data show that SILAC analysis in mouse xenografts is a valuable approach for deciphering tyrosine kinase oncogenic signaling in vivo.

Dataset Information

Oncogenic Activity of Wrap53 in Human Colorectal Cancer In Vitro and in Nude Mouse Xenografts.

Publications

Oncogenic Activity of Wrap53 in Human Colorectal Cancer In Vitro and in Nude Mouse Xenografts.

Similar Datasets

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