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Updated: May 2, 2026
MicroRNA Detection in Prostate Tumors by Quantitative Real-time PCR qPCR
Published on: May 16, 2012
miR-34 cooperates with p53 in suppression of prostate cancer by joint regulation of stem cell compartment
Chieh-Yang Cheng1, Chang-Il Hwang1, David C Corney1
1Department of Biomedical Sciences and Cornell Stem Cell Program, Cornell University, Ithaca, NY 14853, USA.
Abstract:
The miR-34 family was originally found to be a direct target of p53 and is a group of putative tumor suppressors. Surprisingly, mice lacking all mir-34 genes show no increase in cancer formation by 18 months of age, hence placing the physiological relevance of previous studies in doubt. Here, we report that mice with prostate epithelium-specific inactivation of mir-34 and p53 show expansion of the prostate stem cell compartment and develop early invasive adenocarcinomas and high-grade prostatic intraepithelial neoplasia, whereas no such lesions are observed after inactivation of either the mir-34 or p53 genes alone by 15 months of age. Consistently, combined deficiency of p53 and miR-34 leads to acceleration of MET-dependent growth, self-renewal, and motility of prostate stem/progenitor cells. Our study provides direct genetic evidence that mir-34 genes are bona fide tumor suppressors and identifies joint control of MET expression by p53 and miR-34 as a key component of prostate stem cell compartment regulation, aberrations in which may lead to cancer.
Insights
The miR-34 family and p53 jointly suppress prostate cancer by regulating stem cell growth. Their combined loss accelerates tumor formation, challenging previous assumptions about miR-34
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The miR-34 family, direct targets of p53, are considered tumor suppressors.
- Previous studies' physiological relevance is questioned as mir-34 knockout mice show no increased cancer incidence by 18 months.
- The role of miR-34 in cancer, particularly prostate cancer, requires further investigation.
Purpose of the Study:
- To investigate the role of miR-34 in prostate cancer development.
- To determine the combined effect of miR-34 and p53 inactivation on prostate stem cells and cancer formation.
- To elucidate the regulatory mechanisms of prostate stem cell proliferation and motility.
Main Methods:
- Prostate epithelium-specific inactivation of mir-34 and p53 genes in mice.
- Analysis of prostate stem cell compartment expansion.
- Histopathological evaluation for prostatic intraepithelial neoplasia and adenocarcinoma.
- Assessment of MET-dependent growth, self-renewal, and motility of prostate stem/progenitor cells.
Main Results:
- Mice with combined mir-34 and p53 inactivation developed early invasive adenocarcinomas and high-grade prostatic intraepithelial neoplasia.
- Inactivation of either mir-34 or p53 alone did not result in such lesions by 15 months.
- Combined deficiency accelerated MET-dependent growth, self-renewal, and motility of prostate stem/progenitor cells.
Conclusions:
- miR-34 genes function as bona fide tumor suppressors in the prostate.
- Joint control of MET expression by p53 and miR-34 is crucial for regulating the prostate stem cell compartment.
- Aberrations in this regulatory pathway can lead to prostate cancer development.
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