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Updated: May 16, 2026

miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
Evidence for downregulation of the negative regulator SPRED2 in clinical prostate cancer
N Kachroo1, T Valencia, A Y Warren
1Translational Prostate Cancer Group, Hutchison/MRC Research centre, University of Cambridge, Cambridge CB1 0XZ, UK.
Background:
SPRED1 and 2 are key negative regulators of MAPK signalling in mammalian cells. Here, we investigate the expression and functional role of SPREDs in prostate cancer.
Methods:
A transcriptome bank of microdissected grade-specific primary cancers was constructed and interrogated for transcript expression of prostate cancer genes, known negative signalling regulators as well as SPRED1 and 2. The effect of SPRED2 manipulation was tested in in vitro assays.
Results:
In a panel of 5 benign glands and 15 tumours, we observed concomitant downregulation of the negative regulators SEF and DUSP1 in tumours with increasing Gleason grade. Profiling in the same cohorts revealed downregulation of SPRED2 mRNA in tumours compared with benign glands (P<0.05). By contrast, SPRED1 expression remained unchanged. This observation was further validated in two additional separate cohorts of microdissected tumours (total of n=10 benign and n=58 tumours) with specific downregulation of SPRED2 particularly in higher grade tumours. In functional assays, SPRED2 overexpression reduced ERK phosphorylation and inhibited prostate cancer cell proliferation and migration in response to different growth factors and full-media stimulation (P<0.001). Conversely, SPRED2 suppression by siRNA enhanced the mitogenic response to growth factors and full media (P<0.001).
Conclusion:
These data suggest first evidence that SPRED2 is downregulated in prostate cancer and warrants further investigation as a potential tumour-suppressor gene.
Insights
SPRED2, a negative regulator of MAPK signaling, is downregulated in prostate cancer. Its reduced expression correlates with higher tumor grade and promotes cancer cell proliferation, suggesting it may act as a tumor suppressor.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- SPRED1 and SPRED2 are negative regulators of MAPK signaling in mammalian cells.
- Investigating the role of SPRED proteins in prostate cancer progression.
Purpose of the Study:
- To investigate the expression and functional role of SPRED1 and SPRED2 in prostate cancer.
- To determine if SPRED2 acts as a tumor suppressor in prostate cancer.
Main Methods:
- Transcriptome analysis of microdissected, grade-specific prostate cancers.
- In vitro functional assays to assess the effect of SPRED2 manipulation on cancer cell behavior.
Main Results:
- SPRED2 mRNA was downregulated in prostate tumors compared to benign glands, with greater downregulation in higher-grade tumors.
- SPRED2 overexpression inhibited prostate cancer cell proliferation and migration.
- SPRED2 suppression enhanced prostate cancer cell proliferation and migration.
Conclusions:
- SPRED2 is downregulated in prostate cancer, particularly in higher-grade tumors.
- SPRED2 functions as a negative regulator of prostate cancer cell proliferation and migration.
- SPRED2 warrants further investigation as a potential tumor suppressor gene in prostate cancer.
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