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High expression of WISP1 in colon cancer is associated with apoptosis, invasion and poor prognosis.

ABSTRACT: Colon cancer (CC) likes many epithelial-derived cancers, resulting from a complex tumorigenic process. However, the exactly mechanisms of development and progression of CC are still unknown. In this study, integrated analysis in the GSE33113 and Fudan University Shanghai Cancer Center Hospital datasets revealed that WISP1 expression was significantly increased in CC cases, positivity correlated with the advanced pathologic stage and a poor prognosis was more likely in CC patients with higher levels of WISP1. Downregulation of WISP1 inhibited cell proliferation and invasion through increasing apoptosis and blocking cell cycle at G1 phase in CC LOVO and RKO cells. Besides, Gene set enrichment analysis (GSEA) revealed that relative genes involved in the Cell adhesion molecules and Cytokine-cytokine receptor interaction pathways were enriched in WISP1-higher expression patients. Western blot analysis showed that Cell adhesion molecules pathway associated genes (ICAM- 1, VCAM-1, SDC2 and CDH2) and Cytokine-cytokine receptor interaction pathway associated genes (VEGFC, CCL18, CXCR4 and TGFBR1) were also modulated by WISP1 downregulation. Then, we found that the protein ?-catenin was identified as a binding partner of WISP1 and mediated the functions of WISP1 through promoting cell proliferation and invasion in LOVO and RKO cells. Further in vivo tumor formation study in nude mice indicated that inhibition of WISP1 delayed the progress of tumor formation and inhibited PCNA expression. These results indicate that WISP1 could act as an oncogene and may serve as a promising therapeutic strategy for colon cancer.

SUBMITTER: Wu J

PROVIDER: S-EPMC5226551 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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High expression of WISP1 in colon cancer is associated with apoptosis, invasion and poor prognosis.

Wu Jianghong J Long Ziwen Z Cai Hong H Du Chunyan C Liu Xiaowen X Yu Shengjia S Wang Yanong Y

Oncotarget 20160801 31

Colon cancer (CC) likes many epithelial-derived cancers, resulting from a complex tumorigenic process. However, the exactly mechanisms of development and progression of CC are still unknown. In this study, integrated analysis in the GSE33113 and Fudan University Shanghai Cancer Center Hospital datasets revealed that WISP1 expression was significantly increased in CC cases, positivity correlated with the advanced pathologic stage and a poor prognosis was more likely in CC patients with higher lev ...[more]

PMID: 27409174

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Project description:BackgroundHeat shock protein 90 (HSP90) is a highly conserved chaperone with an approximate molecular weight of 90-kDa. It plays a critical role in maintaining stability and homeostasis of oncoproteins, helping cancer cells living in the unsuitable environmental conditions. The current study aims to inquire the difference of HSP90 expression in tumor tissues and normal tissues, analyze the correlation between HSP90 expression and the prognoses of patients with colorectal cancer (CRC), and investigate its role in CRC preliminarily.MethodsOnline analysis of HSP90 mRNA levels in different cancers was firstly done in Gene Expression Profiling Interactive Analysis. Then HSP90 expression was determined by immunohistochemistry between 99 CRC tissues and 81 normal tissues. Chi-square test or Fisher's exact test was used to analyze the relationship between HSP90 and histopathologic characteristics. Kaplan-Meier analysis and Cox's proportional hazards model were also done for further analysis of the prognostic values of HSP90. Pearson's correlation coefficients between HSP90 expression values and other mRNA expression values were calculated based on The Cancer Genome Atlas dataset and bioinformatic analysis was done about these screened genes.ResultsColorectal cancer tissues showed significantly higher expression of HSP90 than normal tissues (55.6% vs. 3.7%, P < 0.0001). Kaplan-Meier curves showed high HSP90 expression was associated with poor prognosis (P = 0.039) in CRC patients, and multivariate Cox proportional hazards regression model analysis also indicated that HSP90 expression (HR = 1.930, 95% CI [1.113-3.349], P = 0.019) linked to poor prognosis. Moreover, 85 genes were correlated with HSP90, which were involved in metabolic process and enriched in pathways of Proteasome and Base excision repair.ConclusionsOur results suggested that HSP90 expression is inversely associated with survival outcomes and could be an independent prognostic factor for CRC patients. It mainly involved in metabolic process and exerted binding and catalytic activities.

Dataset Information

High expression of WISP1 in colon cancer is associated with apoptosis, invasion and poor prognosis.

Publications

High expression of WISP1 in colon cancer is associated with apoptosis, invasion and poor prognosis.

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