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MicroRNAs 221/222 and genistein-mediated regulation of ARHI tumor suppressor gene in prostate cancer
- Source :
- Cancer prevention research (Philadelphia, Pa.). 4(1)
- Publication Year :
- 2010
-
Abstract
- ARHI is an imprinted tumor suppressor gene and is downregulated in various malignancies. However, ARHI expression, function, and mechanisms of action in prostate cancer have not been reported. Here, we report that ARHI mRNA and protein levels were downregulated in prostate cancer tissues compared with adjacent normal tissues. Overexpression of ARHI inhibited cell proliferation, colony formation, invasion, and induced apoptosis. Further studies on a new mechanism of ARHI downregulation showed a significant inverse relationship between ARHI and miR-221 and 222, which were upregulated in prostate cancer cell lines. Transfection of miR-221 and 222 inhibitors into PC-3 cells caused a significant induction of ARHI expression. A direct interaction of miR-221 or 222 with a target site on the 3′UTR of ARHI was confirmed by a dual luciferase pMIR-REPORT assay. Finally, we also found that genistein upregulates ARHI by downregulating miR-221 and 222 in PC-3 cells. In conclusion, ARHI is a tumor suppressor gene downregulated in prostate cancer, and overexpression of ARHI can inhibit cell proliferation, colony formation, and invasion. This study demonstrates for the first time that prostate cancer cells have decreased level of ARHI which could be caused by direct targeting of 3′UTR of ARHI by miR221/222. Genistein, a potential nontoxic chemopreventive agent, restores expression of ARHI and may be an important dietary therapeutic agent for treating prostate cancer. Cancer Prev Res; 4(1); 76–86. ©2010 AACR. Cancer Prev Res; 4(1); 76–86. ©2010 AACR.
- Subjects :
- Male
rho GTP-Binding Proteins
Cancer Research
Tumor suppressor gene
Blotting, Western
Genistein
Apoptosis
Bone Neoplasms
Biology
Article
Immunoenzyme Techniques
chemistry.chemical_compound
Prostate cancer
Downregulation and upregulation
Cell Movement
microRNA
medicine
Cell Adhesion
Anticarcinogenic Agents
Humans
Genes, Tumor Suppressor
Neoplasm Invasiveness
RNA, Messenger
Luciferases
Promoter Regions, Genetic
Cells, Cultured
Tumor Stem Cell Assay
Cell Proliferation
Regulation of gene expression
Cell growth
Reverse Transcriptase Polymerase Chain Reaction
Prostatic Neoplasms
Transfection
DNA Methylation
medicine.disease
Flow Cytometry
Molecular biology
Gene Expression Regulation, Neoplastic
MicroRNAs
Oncology
chemistry
Cancer research
Subjects
Details
- ISSN :
- 19406215
- Volume :
- 4
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cancer prevention research (Philadelphia, Pa.)
- Accession number :
- edsair.doi.dedup.....cd39c7282186cdb75d80ee873eca98c5