Long noncoding RNAs, ENST00000598996 and ENST00000524265, are correlated with favorable prognosis and act as potential tumor suppressors in bladder cancer

Abstract

Bladder cancer (BC) is a serious malignancy worldwide due to its distant metastasis and high recurrence rates. Increasing evidence has indicated that dysregulated long non-coding RNAs (lncRNAs) are involved in tumorigenesis and progression in multiple malignancies. However, their clinical significances, biological functions and molecular mechanisms in BC remain poorly understood. Hence, the present study investigated the expression profile of lncRNAs and mRNAs in five BC tissues and the corresponding adjacent normal specimens using high-throughput RNA sequencing (RNA-seq). A total of 103 differentially expressed (DE) lncRNAs were identified, including 35 upregulated and 68 downregulated ones in BC tissues. Similarly, a total of 2,756 DE-mRNAs were detected, including 1,467 upregulated and 1,289 downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, and lncRNA-miRNA-mRNA network analyses suggested that these dysregulated lncRNAs are potentially implicated in the onset and progression of BC. Subsequently, four lncRNAs (upregulated ENST00000433108; downregulated ENST00000598996, ENST00000524265 and ENST00000398461) and two mRNAs (upregulated CCNB1 and CDK1) in 64 pairs of BC and adjacent normal tissues and four BC cell lines were detected using reverse transcription-quantitative PCR and these results were consistent with the sequencing data. Additionally, Fisher's exact test, Kaplan-Meier plots, and Cox regression analyses were used for elucidating the clinical values of ENST00000598996 and ENST00000524265. Furthermore, a receiver operating characteristic curve was constructed to assess their diagnostic values. The low expression level of ENST00000598996 and ENST00000524265 was correlated with unfavorable clinicopathological parameters, and shorter progression-free and overall survival time, whereas, ENST00000433108 was not associated with either. The in vitro functional experiments also revealed that the overexpression of ENST00000598996 and ENST00000524265 decreased the proliferation, migration, and invasion abilities of BC cells. Collectively, the results of the present study provide a novel landscape of lncRNA and mRNA expression profiles in BC. In addition, the results also indicated that ENST00000598996 and ENST00000524265 may serve as tumor suppressors, potential diagnostic biomarkers and prognostic predictors for patients with BC.

Comprehensive analysis of Transcription Factors identified novel prognostic biomarker in human bladder cancer

“…Survival analysis of these identified TFs presented that the high risk of the five-TFs combination model was associated with poor overall survival. Chong Shen et al identified a potential prognostic biomarker, LncRNA ENST00000598996 and ENST00000524265, by WGCNA and PPI network analysis of BCa 8 . And previous studies have reported that lncRNA XIST 21 , MAGI2‑AS3 22 and ADAMTS9‑AS2 23 are prognostic biomarkers of these patients with BCa and plays a critical role in BCa progression via various tumor-related pathways.…”

“…However, the recent research on the genetic characterization of bladder cancer has turned to the molecular therapy. The limited treatment options emphasize the demand for new and effective prognostic biomarkers and new therapeutic modalities 8 .…”

Detection of Novel Urine Markers Using Immune Complexome Analysis in Bladder Cancer Patients: A Preliminary Study

“…Therefore, understanding the pathological mechanisms of tumor progression and urinary tract recurrence in patients with BC is important to improve outcomes. In previous reports, various factors have been reported as useful predictive markers of clinical outcomes, including recurrence in BC patients (3)(4)(5). At present, to predict and diagnose urinary tract recurrence in NMIBC, various new methods and tools are being developed and approved around the world (6,7).…”