Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Song, B. et al.

miR-192 Regulates dihydrofolate reductase and cellular proliferation through the p53-microRNA circuit.

PURPOSE: The purpose of this study is to investigate the molecular mechanism of miR-192 in colon cancer. EXPERIMENTAL DESIGN: Human colon cancer cell lines with different p53 status were used as our model system to study the effect of miR-192 on cell proliferation, cell cycle control, and mechanism of regulation. RESULTS: Our results show that one of the key miR-192 target genes is dihydrofolate reductase (DHFR). miR-192 affects cellular proliferation through the p53-miRNA circuit. Western immunoblot analyses indicated that the expression of DHFR was significantly decreased by miR-192. Further investigation revealed that such suppression was due to translational arrest rather than mRNA degradation. More profound inhibition of cellular proliferation was observed by ectopic expression of miR-192 in colon cancer cell lines containing wild-type p53 than cells containing mutant p53. Thus, the effect of miR-192 on cellular proliferation is mainly p53 dependent. Overexpression of miR-192 triggered both G1 and G2 arrest in HCT-116 (wt-p53) cells but not in HCT-116 (null-p53) cells. The cell cycle checkpoint control genes p53 and p21 were highly overexpressed in cells that overexpressed miR-192. Endogenous miR-192 expression was increased in HCT-116 (wt-p53) and RKO (wt-p53) cells treated with methotrexate, which caused an induction of p53 expression. Chromatin immunoprecipitation-quantitative reverse transcription-PCR analysis revealed that the p53 protein interacted with the miR-192 promoter sequence. CONCLUSION: These results indicate that miR-192 may be another miRNA candidate that is involved in the p53 tumor suppressor network with significant effect on cell cycle control and cell proliferation.[1]

References

miR-192 Regulates dihydrofolate reductase and cellular proliferation through the p53-microRNA circuit. Song, B., Wang, Y., Kudo, K., Gavin, E.J., Xi, Y., Ju, J. Clin. Cancer Res. (2008) [Pubmed]

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