Comprehensive analysis of aberrantly expressed profiles of lncRNAs and miRNAs with associated ceRNA network in muscle-invasive bladder cancer

Abstract

Although initially thought to be transcriptional noise, long noncoding RNAs (lncRNAs) are gaining increased attention in human cancers as its diversity function. At present, lncRNAs are regarded as the main part of competing endogenous RNA (ceRNA) network due to its regulation on protein-coding gene expression by acting as miRNA sponges. However, functional roles of lncRNA-mediated ceRNAs in muscle-invasive bladder cancer remain unclear. To clarify relevant potential mechanisms, here we comprehensively compared the expression profiles of mRNAs, lncRNAs and miRNAs between 322 muscle-invasive bladder cancer tissues and 19 non-tumor bladder tissues, based on the Cancer Genome Atlas (TCGA). A total of 22 lncRNAs were identified as aberrantly expressed and had correlations with tumorigenesis and/or progression of muscle-invasive bladder cancer (|log2FoldChange| > 1.5, corrected P value < 0.01). 6 out of the 22 dysregulated lncRNAs functioned as prognostic biomarkers for patients with muscle-invasive bladder cancer according to the overall survival analysis (P value < 0.05). Finally, a dysregulated lncRNA-associated ceRNA network was successfully constructed, which inculdes five muscle-invasive bladder cancer-specific lncRNAs, nine miRNAs and 32 mRNAs. In summary, our study identified novel lncRNAs as candidate prognostic biomarkers and potential therapeutic targets for muscle-invasive bladder cancer, based on large-scale sample size. More importantly, the newly identified ceRNA network will be beneficial for improving the understanding of lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of muscle-invasive bladder cancer.

RNA-Sequencing Data Reveal a Prognostic Four-lncRNA-Based Risk Score for Bladder Urothelial Carcinoma: An in Silico Update

“…Study population RNA-sequencing reads per kilobase million (RPKM) data of patients with BLCA were obtained from TCGA [12,25]. The cohort contained 433 samples, including 414 tumor tissue samples and 19 non-tumor adjacent bladder tissue samples.…”

“…Long non-coding RNAs (lncRNAs) are a class of RNAs lacking protein-coding function which were initially regarded as "junk RNA" [11,12]. It has been experimentally validated that lncRNAs are involved in the etiology and pathogenesis of various cancers, including BLCA [13][14][15][16][17][18][19][20].…”

“…It has been experimentally validated that lncRNAs are involved in the etiology and pathogenesis of various cancers, including BLCA [13][14][15][16][17][18][19][20]. The recent advances in high-throughput data technologies, including RNAsequencing and microarrays, has guided the identification of lncRNAs for prospective clinical application in BLCA [12,[21][22][23]. However, most previous studies focused on the clinical value of individual lncRNAs, which has limited potential for future clinical application.…”

lncRNA TUG1-Mediated Mir-142-3p Downregulation Contributes to Metastasis and the Epithelial-to-Mesenchymal Transition of Hepatocellular Carcinoma by Targeting ZEB1

“…As a group of ncRNAs, long noncoding RNAs (lncRNAs) act as competing endogenous RNAs (ceRNAs) by binding with miRNAs Yang et al [18,19]. For instance, lncRNA CCAT1 promotes gallbladder cancer development by negatively modulating miRNA-218-5p Ma et al [20]; lncRNA growth-arrest specific 5 (GAS5) inhibits tumorigenesis and enhances radiosensitivity in NSCLC by suppressing miR-135b expression Xue et al [16].…”

Dysregulated lncRNA-UCA1 contributes to the progression of gastric cancer through regulation of the PI3K-Akt-mTOR signaling pathway

“…LncRNAs, which are more than 200 bases in length with little or no protein coding capacity, regulate protein expression through promotion of translation or indirect degradation of RNA transcripts in a sequence specific manner [4][5][6]. Recently, increasing studies have reported that lncRNAs are aberrantly expressed in many human cancers [7][8][9]. Thus, lncRNA functions may play important roles in the progression and metastasis of cancers.…”