Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA303182 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2954330.fastq.gz | Fastqsanger.gz | |||
| SRR2954331.fastq.gz | Fastqsanger.gz | |||
| SRR2954332.fastq.gz | Fastqsanger.gz | |||
| SRR2954333.fastq.gz | Fastqsanger.gz |
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Project description:Recent studies demonstrate both basal and luminal cells of the prostate gland can initiate tumorigenesis upon oncogenic transformation. However, it remains unclear how molecular mechanisms operating within each cell lineage contribute to the initiation and progression of the prostate cancer. Here we investigate functions of individual miRNAs using genetically engineered mouse models. By both quantitative miR-Seq and in situ hybridization, we identify microRNA-205 (miR-205) as the most highly expressed miRNA and specific to the basal cells in the prostate. MicroRNA-205 expression is further elevated in the basal cells in the well-established Pten null tumorigenic mouse model. To investigate the role of miR-205 in Pten-deletion mediated tumorigenesis, we generated a Pten/miR-205 double knockout mouse model. Concurrent deletion of both miR-205 and Pten significantly compromised tumor progression in both basal and luminal compartments. We observed significantly reduced tumor size and compromised proliferation in both basal and luminal cells. We have previously demonstrated a critical requirement of miR-205 for maintaining the PI(3)K signaling and pAkt levels in skin stem cells. Consistent with this role, we observed strong reduction of pAkt and significantly increased cellular senescence in the basal cells of the dKO, compared to the Pten KO alone. These results suggest that miR-205 is cell-autonomously required for the tumorigenesis of the basal cells. Taken together, we have identified miR-205 as an important regulator in prostate cancer. Our study also reveals an essential and unexpected role of the basal cells for promoting prostate tumorigenesis.
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Project description:The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here, we describe a whole-genome transcriptome analysis of human benign prostatic basal and luminal populations by using deep RNA sequencing. Combined with comprehensive molecular and biological characterizations, we show that the differential gene expression profiles account for their distinct functional phenotypes. Strikingly, in contrast to luminal cells, basal cells preferentially express gene categories associated with stem cells, neural and neuronal development and RNA processing. Consistent with their expression profiles, basal cells functionally exhibit intrinsic stem-like and proneural properties with enhanced ribosome RNA (rRNA) transcription activity. Of clinical relevance, the treatment failed castration-resistant and anaplastic prostate cancers molecularly resemble a basal-like phenotype. Therefore, we link the cell-type specific gene signatures to subtypes of prostate cancer development, and identify genes associated with patient clinical outcome. Human total RNA profiles of 3 pairs of benign prostatic basal and luminal populations freshly purified from prostate tissues of three prostate cancer patients by deep RNA-seq.
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Project description:The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here, we describe a whole-genome transcriptome analysis of human benign prostatic basal and luminal populations by using deep RNA sequencing. Combined with comprehensive molecular and biological characterizations, we show that the differential gene expression profiles account for their distinct functional phenotypes. Strikingly, in contrast to luminal cells, basal cells preferentially express gene categories associated with stem cells, neural and neuronal development and RNA processing. Consistent with their expression profiles, basal cells functionally exhibit intrinsic stem-like and proneural properties with enhanced ribosome RNA (rRNA) transcription activity. Of clinical relevance, the treatment failed castration-resistant and anaplastic prostate cancers molecularly resemble a basal-like phenotype. Therefore, we link the cell-type specific gene signatures to subtypes of prostate cancer development, and identify genes associated with patient clinical outcome.
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