Screening biomarkers of bladder cancer using combined miRNA and mRNA microarray analysis

Abstract

Biomarkers, such as microRNAs (miRNAs) may be useful for the diagnosis of bladder cancer. In order to understand the molecular mechanisms underlying bladder cancer, differentially expressed miRNAs (DE-miRNAs) and their target genes in bladder cancer were analyzed. In the present study, miRNA and mRNA expression profiles (GSE40355) were obtained from the Gene Expression Omnibus. These consisted of healthy bladder samples (n=8) and urothelial carcinoma samples (low-grade, n=8 and high-grade, n=8). DE-miRNAs and differentially expressed genes (DEGs) were identified using the limma package and the Benjamin and Hochberg method from the multtest package in R. Target genes of DE-miRNAs were screened. Associations between DEGs were investigated using STRING, and an interaction network was constructed using Cytoscape. Functional and pathway enrichment analyses were performed for DEGs from the interaction network. 87 DE-miRNAs and 2058 DEGs were screened from low-grade bladder cancer samples, and 40 DE-miRNAs and 2477 DEGs were screened from high-grade bladder cancer samples. DE-target genes were significantly associated with the regulation of cell apoptosis. Bladder cancer, non-small cell lung cancer and pancreatic cancer biological pathways were found to be enriched. The results of the present study demonstrated that E2F transcription factor 1, which is targeted by miR-106b, and cyclin-dependent kinase inhibitor 2A (CDKN2A) and V-Erb-B2 avian erythroblastic leukemia viral oncogene homolog-2, which are targeted by miR-125b, participate in the bladder cancer pathway. In conclusion, DE-miRNAs in bladder cancer tissue samples and DE-targeted genes, such as miR-106b and CDKN2A, which were identified in the present study, may provide the basis for targeted therapy for breast cancer and enhance understanding of its pathogenesis.

From big data to diagnosis and prognosis: gene expression signatures in liver hepatocellular carcinoma

“…Zhang et al (2016b) demonstrated that E2F1-mediated overexpression of LINC00668 promotes or facilitates cell proliferation and cell cycle in gastric cancer. The functions of E2F1 as a target for other molecules have also been extensively reported, such as miR-106b in bladder cancer (Jin et al, 2015b), miR-136 in glioma cells (Chen et al, 2014), miR-331-3p in gastric cancer (Guo et al, 2010) and so forth.…”

Gene Expression and Regulatory Webwork of POLR2K in Bladder Carcinogenesis by Integrated Bioinformatics Approaches

“…Abnormal E2F1 expression proactively is related to the tumor formation and progression of BLCA [37]. There is one study has published that elevated levels of E2F1 is involved in shorter survival of bladder cancer patients [38], and another study showed that the POLR2K network of transcription factor targets is related to E2F1 [39]. Thus, these analyses suggest that E2F1 may be a critical target of POLR2K which modulates cell cycle and cancer progression in BLCA patients by acting through E2F1 transcription factor.…”

Peer Review #1 of "From big data to diagnosis and prognosis: gene expression signatures in liver hepatocellular carcinoma (v0.1)"

“…Recently, studies of E2F1 have uncovered its critical roles in the control of transcription, proliferation and apoptosis (DeGregori & Johnson 2006;Muller et al 2001;O'Donnell et al 2005), and accumulating evidence showed that E2F1, a fundamental biological regulator with the ability to activate transcription in downstream genes, was also involved in the regulation of other molecules, such as miRNAs and lncRNAs. For instance, Kathryn, et al (O'Donnell et al 2005) cancer (Jin et al 2015b), miR-136 in glioma cells (Chen et al 2014), miR-331-3p in gastric cancer (Guo et al 2010) and so forth.…”