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miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer
Zhou Du1,2, Tong Sun3,4,5, Ezgi Hacisuleyman6,7,8
1Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Shanghai 200433, China.
Abstract:
Mounting evidence suggests that long noncoding RNAs (lncRNAs) can function as microRNA sponges and compete for microRNA binding to protein-coding transcripts. However, the prevalence, functional significance and targets of lncRNA-mediated sponge regulation of cancer are mostly unknown. Here we identify a lncRNA-mediated sponge regulatory network that affects the expression of many protein-coding prostate cancer driver genes, by integrating analysis of sequence features and gene expression profiles of both lncRNAs and protein-coding genes in tumours. We confirm the tumour-suppressive function of two lncRNAs (TUG1 and CTB-89H12.4) and their regulation of PTEN expression in prostate cancer. Surprisingly, one of the two lncRNAs, TUG1, was previously known for its function in polycomb repressive complex 2 (PRC2)-mediated transcriptional regulation, suggesting its sub-cellular localization-dependent function. Our findings not only suggest an important role of lncRNA-mediated sponge regulation in cancer, but also underscore the critical influence of cytoplasmic localization on the efficacy of a sponge lncRNA.
Insights
Long noncoding RNAs (lncRNAs) act as microRNA sponges, regulating prostate cancer genes. Their tumor-suppressive function and localization are critical for efficacy.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Long noncoding RNAs (lncRNAs) are increasingly recognized for regulatory roles.
- lncRNAs can function as microRNA sponges, sequestering microRNAs from protein-coding transcripts.
- The role of lncRNA-mediated sponge regulation in cancer remains largely unexplored.
Purpose of the Study:
- To identify lncRNA-mediated sponge regulatory networks in prostate cancer.
- To investigate the functional significance and targets of lncRNA sponges in cancer.
- To explore the dual functions of lncRNAs based on subcellular localization.
Main Methods:
- Integrated analysis of sequence features and gene expression profiles of lncRNAs and protein-coding genes in tumors.
- Identification of a lncRNA-mediated sponge regulatory network.
- Functional validation of specific lncRNAs in prostate cancer models.
Main Results:
- A novel lncRNA-mediated sponge regulatory network impacting prostate cancer driver genes was identified.
- Two lncRNAs, TUG1 and CTB-89H12.4, were confirmed to have tumor-suppressive functions and regulate PTEN expression.
- TUG1 exhibits context-dependent functions, including PRC2-mediated transcriptional regulation and microRNA sponging, influenced by its subcellular localization.
Conclusions:
- lncRNA-mediated sponge regulation plays a significant role in prostate cancer.
- Subcellular localization is a critical determinant of a sponge lncRNA's efficacy.
- These findings highlight new therapeutic targets and regulatory mechanisms in prostate cancer.
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