Back to Search
Start Over
A FTH1 gene:pseudogene:microRNA network regulates tumorigenesis in prostate cancer
- Source :
- Nucleic Acids Research
- Publication Year :
- 2017
-
Abstract
- Non-coding RNAs play a vital role in diverse cellular processes. Pseudogenes, which are non-coding homologs of protein-coding genes, were once considered non-functional evolutional relics. However, recent studies have shown that pseudogene transcripts can regulate their parental transcripts by sequestering shared microRNAs (miRNAs), thus acting as competing endogenous RNAs (ceRNAs). In this study, we utilize an unbiased screen to identify the ferritin heavy chain 1 (FTH1) transcript and multiple FTH1 pseudogenes as targets of several oncogenic miRNAs in prostate cancer (PCa). We characterize the critical role of this FTH1 gene:pseudogene:miRNA network in regulating tumorigenesis in PCa, whereby oncogenic miRNAs downregulate the expression of FTH1 and its pseudogenes to drive oncogenesis. We further show that impairing miRNA binding and subsequent ceRNA crosstalk completely rescues the slow growth phenotype in vitro and in vivo. Our results also demonstrate the reciprocal regulation between the pseudogenes and intracellular iron levels, which are crucial for multiple physiological and pathophysiological processes. In summary, we describe an extensive gene:pseudogene network comprising multiple miRNAs and multiple pseudogenes derived from a single parental gene. The network could be regulated through multiple mechanisms to modulate iron storage in various signaling pathways, the deregulation of which results in PCa development and progression.
- Subjects :
- 0301 basic medicine
Male
Carcinogenesis
Pseudogene
Iron
Mice, Nude
MiRNA binding
Computational biology
Biology
RNA Prot Comp
03 medical and health sciences
Cell Line, Tumor
microRNA
Genetics
Animals
Humans
Genes, Tumor Suppressor
P-Chloroamphetamine
Gene
FTH1
Competing endogenous RNA
Prostatic Neoplasms
Phenotype
MicroRNAs
030104 developmental biology
Ferritins
Mutation
Oxidoreductases
Pseudogenes
Subjects
Details
- ISSN :
- 13624962
- Volume :
- 46
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Nucleic acids research
- Accession number :
- edsair.doi.dedup.....54fb0907559343982c9ffc2ee9c0cff7