Investigation of key miRNAs and target genes in bladder cancer using miRNA profiling and bioinformatic tools

Abstract

Despite the association of several miRNAs with bladder cancer, little is known about the miRNAs' regulatory networks. In this study, we aimed to construct potential networks of bladder-cancer-related miRNAs and their known target genes using miRNA expression profiling and bioinformatics tools and to investigate potential key molecules that might play roles in bladder cancer regulatory networks. Global miRNA expression profiles were obtained using microarray followed by RT-qPCR validation using two randomly selected miRNAs. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of three selected KEGG pathways were visualized by Cytoscape software. We finally gained 19 deregulated miRNAs, including 5 ups- and 14 down regulated in 27 bladder-cancer tissue samples and 8 normal urothelial tissue samples. The enrichment results of deregulated miRNAs and known target genes showed that most pathways were related to cancer or cell signaling pathways. We determined the hub CDK6, BCL2, E2F3, PTEN, MYC, RB, and ERBB3 target genes and hub hsa-let-7c, hsa-miR-195-5p, hsa-miR-141-3p, hsa-miR-26a-5p, hsa-miR-23b-3p, and hsa-miR-125b-5p miRNAs of the constructed networks. These findings provide new insights into the bladder cancer regulatory networks and give us a hypothesis that hsa-let-7c, hsa-miR-195-5p, and hsa-miR-125b-5p, along with CDK4 and CDK6 genes might exist in the same bladder cancer pathway. Particularly, hub miRNAs and genes might be potential biomarkers for bladder cancer clinics.

Comprehensive circular RNA profiling reveals the regulatory role of the circRNA-100338/miR-141-3p pathway in hepatitis B-related hepatocellular carcinoma

“…Among all the miRNAs identified, miR-141-3p is particularly worth investigating, due to the following reasons: (1) miR-141-3p binding sites of high complementarity were found in hsa_circRNA_100338 with a high prediction score, suggesting a strong likelihood of miR-141-3p being a bona fide circRNA target (Fig. 4B); (2) miR-141-3p is widely dysregulated in several cancer types, such as colorectal cancer, bladder cancer, ovarian cancer and liver cancer 21–25 ; and (3) miR-141-3p has previously been implicated as a tumour or metastasis suppressor in various types of cancer cells 24, 26 . These lines of evidence suggest that circRNA_100338 may interact with miR-141-3p to regulate the gene expression necessary for HCC carcinogenesis.

Figure 4circRNA_100338 interacts with miR-141 in HCC.

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Aberrantly expressed microRNAs in bladder cancer and renal cell carcinoma

“…[11][12][13][14][15][16][17] The analysis platforms varied between studies. Two recent signatures were constructed from deep sequencing, and the other five signatures were 24,25 In this review, to clearly summarize these miRNA signatures, we focused on commonly downregulated miRNAs or upregulated miRNAs regardless of the platforms and backgrounds of clinical tissues.…”

“…In this review, we summarize aberrantly expressed miRNAs based on current BC and RCC miRNA signatures. [11][12][13][14][15][16][17][18][19][20][21][22][23] We discuss the dysregulated expression of the miR-200 family and miR-200 family target genes in BC and RCC.…”

The Identification of Differentially Expressed Genes of Human Prolactinoma by Microarray

“…The background network includes 80,980 edges and 13,361 nodes. We regard red nodes as up-regulated genes, yellow nodes as down-regulated genes and grey nodes as other nodes (Isserlin et al, 2011;Stark et al, 2011;Salwinski et al, 2004;Peri et al, 2003;Aranda et al, 2010;Licata et al, 20 12;Pagel et al, 2005;Beuming et al, 2005;Yu et al, 2012;Canturk et al, 2014;Wang et al, 2014).…”