Related Experiment Videos
Identification of long non-coding RNAs that stimulate cell survival in bladder cancer
Aleksandra M Dudek1, Sabrina J Boer1, Nanda Boon1
1Department of Urology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
Abstract:
For many years, research on the biology underlying bladder cancer focused on protein-coding genes which cover only about 3% of the human genome. Recently, it was discovered that a large part of the human genome is actively transcribed as long non-coding RNAs (lncRNAs). LncRNAs are master regulators of gene expression and several lncRNAs were shown to play a role in bladder cancer development and progression. Here, we analyzed lncRNA expression in muscle-invasive bladder cancer (MIBC) using the MiTranscriptome database of cancer lncRNA expression profiles, and we studied their function in bladder cancer-derived tumor cells. Analysis of the MiTranscriptome lncRNA expression data revealed four MIBC subgroups, which partially overlapped with the four mRNA clusters identified by The Cancer Genome Atlas consortium. Up-regulation of three lncRNAs CAT266, CAT1297, and CAT1647 in bladder cancer, in comparison to normal urothelium, was confirmed in an independent series of normal, non-muscle invasive (NMIBC) and MIBC tissue samples. Furthermore, expression levels of CAT1297 were found to be correlated with disease-free and overall survival in MIBC. Knockdown of CAT266, CAT1297, and CAT1647 decreased cell viability and colony formation, due to the induction of apoptosis. In conclusion, our data show that lncRNAs expression is de-regulated in MIBC and three aberrantly expressed transcripts regulate proliferation and apoptosis. Our data indicate that lncRNAs play an important role in MIBC development and progression and are a treasure chest for the discovery of new biomarkers.
Insights
Long non-coding RNAs (lncRNAs) are key in bladder cancer. Aberrant expression of three lncRNAs (CAT266, CAT1297, CAT1647) impacts cell viability and apoptosis, highlighting their role in muscle-invasive bladder cancer progression and potential as biomarkers.
Area of Science:
- Genomics
- Molecular Biology
- Oncology
Background:
- Research traditionally focused on protein-coding genes, overlooking the vast non-coding regions of the genome.
- Long non-coding RNAs (lncRNAs) are emerging as critical regulators of gene expression.
- Several lncRNAs have been implicated in the development and progression of bladder cancer.
Purpose of the Study:
- To analyze lncRNA expression profiles in muscle-invasive bladder cancer (MIBC).
- To investigate the functional roles of specific lncRNAs in bladder cancer cell lines.
- To identify potential lncRNA biomarkers for bladder cancer.
Main Methods:
- Utilized the MiTranscriptome database for lncRNA expression analysis in MIBC.
- Validated lncRNA expression in independent tissue samples (normal, NMIBC, MIBC).
- Performed functional studies, including knockdown experiments, in bladder cancer cells.
Main Results:
- Identified four MIBC subgroups based on lncRNA expression, partially correlating with mRNA clusters.
- Confirmed up-regulation of lncRNAs CAT266, CAT1297, and CAT1647 in bladder cancer tissues.
- Demonstrated that CAT1297 expression correlates with patient survival and that knockdown of these three lncRNAs reduces cell viability and colony formation by inducing apoptosis.
Conclusions:
- lncRNA expression is significantly altered in MIBC.
- Aberrantly expressed lncRNAs CAT266, CAT1297, and CAT1647 play crucial roles in regulating proliferation and apoptosis.
- These findings underscore the importance of lncRNAs in MIBC pathogenesis and suggest their potential as novel diagnostic and prognostic biomarkers.