Our group recently developed a transgenic murine model of prostate cancer involving prostate-specific Pten deletion and forced expression of MYC under the control of the Hoxb13 promoter.
Together, our results suggest that rs339331 affects prostate cancer risk by altering RFX6 expression through a functional interaction with the prostate cancer susceptibility gene HOXB13.
These data show that combined MYC activation and Pten loss driven by the Hoxb13 regulatory locus synergize to induce genomic instability and aggressive prostate cancer that phenocopies the human disease at the histologic and genomic levels.
Among the HOTBIN10 genes, AURKB and MELK expression correlates with HOXB13 expression in CTCs of mCRPC patients who did not respond to abiraterone (ABR), suggesting that AURKB inhibitors could be used additionally against high-risk HOXB13-positive metastatic prostate cancers.
We also report results for a previously described HOXB13 variant (rs138213197[T]), confirming it as a prostate cancer risk variant in populations from across Europe.
Quantitative RT-PCR demonstrated the specificity of expression of HOXB13 in prostate tissue and revealed its ubiquitous expression in a series of 37 primary prostate cancers and 20 normal prostates.
For example, a recent study suggested that one cannot adequately impute the HOXB13 G84E mutation associated with prostate cancer risk (carrier frequency of 0.0034 in European ancestry participants in the 1000 Genomes Project).
The mail goal of this research was to study the functional role of Circ-ITCH gene in prostate cancer and to illuminate the function role of circ-ITCH gene in prostate cancer by targeting miR-17-5p/HOXB13.
These results confirm the association of a rare HOXB13 mutation with PC in the general population and suggest that this variant may be associated with features of more aggressive disease.
Results from this study implicated a novel effect of ATRA in inhibition of the growth of AR(-) resistant human prostate cancer cells through alteration of HOXB13 expression as a result of epigenetic modifications.
While the HOXB13G84E mutation may be rare, there may be a future role in genetic testing for this mutation after further studies of clinical utility in assessing prostate cancer risk.
To confirm this association in a screening setting, we conducted a case-control study and sequenced germline DNA from peripheral leukocytes of 1843 men diagnosed with prostate cancer (case subjects) and 2225 men without prostate cancer (control subjects) for mutations in HOXB13.
This study has also shown that the majority of hereditary prostate cancers due to the HOXB13 missense mutation are 'sporadic' in the sense that unselected cases with the missense mutation do not typically report having a family history of prostate cancer.