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Biochem Biophys Res Commun. 2011 Mar 25;406(4):552-7. doi: 10.1016/j.bbrc.2011.02.086. Epub 2011 Feb 23.

MicroRNA 421 suppresses DPC4/Smad4 in pancreatic cancer.

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Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.


MicroRNAs (miRNAs) have emerged as important regulators in the development of pancreatic cancer and may be a valuable therapeutic application. DPC4/Smad4 is a critical tumor suppressor involved in the progression of pancreatic cancer, but few studies have been conducted to determine its relationship with miRNAs. In this study, we identify miR-421 as a potential regulator of DPC4/Smad4. We find that in human clinical specimens of pancreatic cancer miR-421 is aberrantly upregulated while DPC4/Smad4 is strongly repressed, and their levels of expression are inversely correlated. Moreover, ectopic expression of miR-421 significantly decreases DPC4/Smad4 protein level in pancreatic cancer cell lines and simultaneously promotes cell proliferation and colony formation in vitro. Our findings identify miR-421 as a potent regulator of DPC4/Smad4, which may provide a novel therapeutic strategy for treatment of DPC4/Smad4-driven pancreatic cancer.

[Indexed for MEDLINE]

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