Dataset Information

Endogenous BTG2 expression stimulates migration of bladder cancer cells and correlates with poor clinical prognosis for bladder cancer patients.

ABSTRACT:

Background

The B-cell translocation gene 2 (BTG2) is considered to act as a tumour-suppressor gene because of its antiproliferative and antimigratory activities. Higher levels of BTG2 expression in tumour cells have been linked to a better clinical outcome for several cancer entities. Here, we investigated the expression and function of BTG2 in bladder cancer.

Methods

The expression of BTG2 in bladder cancer cells was silenced by RNA interference. Cell motility was investigated by wound healing and Boyden chamber assays. The protein expression of BTG2 in bladder cancer was studied by immunohistochemistry.

Results

We observed that targeted suppression of BTG2 by RNA interference did not result in growth stimulation but led to a substantial inhibition of bladder cancer cell motility. Tissue microarray analyses of bladder cancer cystectomy specimens revealed that higher BTG2 expression levels within the tumours correlated strongly with a decreased cancer-specific survival for bladder cancer patients.

Conclusion

These results indicate that endogenous BTG2 expression contributes to the migratory potential of bladder cancer cells. Moreover, high levels of BTG2 in bladder cancers are linked to decreased cancer-specific survival. These findings question the conception that BTG2 generally acts as a tumour suppressor and typically represents a favourable clinical marker for cancer patients.

SUBMITTER: Wagener N

PROVIDER: S-EPMC3590653 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Publications

Endogenous BTG2 expression stimulates migration of bladder cancer cells and correlates with poor clinical prognosis for bladder cancer patients.

Wagener N N Bulkescher J J Macher-Goeppinger S S Karapanagiotou-Schenkel I I Hatiboglu G G Abdel-Rahim M M Abol-Enein H H Ghoneim M A MA Bastian P J PJ Müller S C SC Haferkamp A A Hohenfellner M M Hoppe-Seyler F F Hoppe-Seyler K K

British journal of cancer 20130108 4

<h4>Background</h4>The B-cell translocation gene 2 (BTG2) is considered to act as a tumour-suppressor gene because of its antiproliferative and antimigratory activities. Higher levels of BTG2 expression in tumour cells have been linked to a better clinical outcome for several cancer entities. Here, we investigated the expression and function of BTG2 in bladder cancer.<h4>Methods</h4>The expression of BTG2 in bladder cancer cells was silenced by RNA interference. Cell motility was investigated by ...[more]

PMID: 23299537

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Project description:BackgroundIGF2BP3 expression is associated with poor prognosis in cancers of multiple tissue origins. However, the precise mechanism of its co-carcinogenic action in bladder cancer is unknown.MethodsWe aimed to demonstrate the relationship between IGF2BP3 expression and pan-cancer using The Cancer Genome Atlas (TCGA) database. We next validated IGF2BP3 expression in the Gene Expression Omnibus (GEO) database (GSE3167). Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic values of IGF2BP3. Cox and logistic regression were used to explore the factors affecting the prognosis. Protein-protein interactions (PPIs) network was constructed by STRING. Enrichment analyses were performed to infer involved pathways and functional categories of IGF2BP3 using the cluster Profiler package. We applied single-sample gene set enrichment analysis (ssGSEA) algorithm and TIMER database to evaluate the expression level of immune genes.ResultsPan-cancer analyses reveal that IGF2BP3 was higher in most cancer types, including bladder cancer, and the same results were found in GSE3167. The area under the ROC curve of IGF2BP3 was 0.736, which indicated that IGF2BP3 may be a potential diagnostic biomarker. High IGF2BP3 expression was associated with poorer overall survival (OS) (P = 0.015). For validation, we collected 95 bladder cancer samples and found that IGF2BP3 expression was higher in bladder cancer tissues than that in non-tumor bladder tissues by immunohistochemistry staining. We found a positive correlation between the expression level of IGF2BP3 and the clinical stage of bladder cancer. Immunocyte infiltration analysis showed that high IGF2BP3 expression was correlated with regulating the infiltration level of immune cell, including neutrophil cells and macrophages. IGF2BP3 promotes migration and invasion of bladder cancer cells, while IGF2BP3 inhibition had the opposite effects. Higher IGF2BP3 expression was closely associated with advanced TNM stage.ConclusionIGF2BP3 overexpression was related to disease progression and poor prognosis, as well as infiltration of immune cells in bladder cancer. IGF2BP3 can be a promising independent prognostic biomarker and potential treatment target for bladder cancer.

Project description:Growing evidence has indicated that circular RNAs (circRNAs) play crucial roles in multiple biological processes. However, alterations in circRNA profiles during bladder cancer progression and the clinical significance thereof remain unclear. Therefore, high-throughput RNA sequencing was conducted to identify circRNA and mRNA profiles in five pairs of bladder cancer tissues and adjacent noncancerous tissues. A total of 87 differentially expressed circRNAs and 2756 mRNAs were detected in above bladder cancer samples compared with paired noncancerous samples. Functional enrichment analyses, circRNA-microRNA-mRNA, and protein-protein interaction networks revealed that these dysregulated circRNAs were potentially involved in carcinogenesis and evolution of bladder cancer. Subsequently, the differential expression of eight circRNAs was detected by real-time qPCR. Hsa_circ_0003141 and hsa_circ_0008039 were significantly upregulated as well as hsa_circ_0026782, hsa_circ_0077837, hsa_circ_0004826, and hsa_circ_0001946 were significantly downregulated among validation of 70 matched bladder cancer tissues (≥75%). Moreover, hsa_circ_0077837 and hsa_circ_0004826 were also verified as markedly downregulated in four bladder cancer cells (100%). Naturally, hsa_circ_0077837 and hsa_circ_0004826 were also demonstrated using RNase-R+ resistance experiments. In addition, Fisher's exact test, Kaplan-Meier plots, Cox regression analyses, and receiver operating characteristic curve was performed to assess their clinical value. Downregulation of hsa_circ_0077837 and hsa_circ_0004826 all was significantly correlated with worse clinicopathological features and poor prognosis of bladder cancer patients. The area under the receiver operating characteristic curve of them was 0.775 (P < .0001) and 0.790 (P < .0001), respectively. Not surprisingly, in vitro functional experiments also demonstrated that the overexpression of hsa_circ_0077837 and hsa_circ_0004826 significantly weakened the proliferation, migration, and invasion of bladder cancer cells. Overall, hsa_circ_0077837 and hsa_circ_0004826 might act as tumor suppressors in the bladder cancer progression and serve as a potential biomarker for the diagnosis, prognosis, and therapy of bladder cancer.

Dataset Information

Endogenous BTG2 expression stimulates migration of bladder cancer cells and correlates with poor clinical prognosis for bladder cancer patients.

Background

Methods

Results

Conclusion

Publications

Endogenous BTG2 expression stimulates migration of bladder cancer cells and correlates with poor clinical prognosis for bladder cancer patients.

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