Article

MicroRNA 483-3p suppresses the expression of DPC4/Smad4 in pancreatic cancer [J]

Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
FEBS letters (Impact Factor: 3.34). 01/2011; 585(1):207-13. DOI: 10.1016/j.febslet.2010.11.039
Source: PubMed

ABSTRACT Both deregulation of tumor-suppressor genes and misexpression of microRNAs (miRNAs) have been implicated in the development of pancreatic cancer, but their relationship during this process remains less clear. Here, we report that the expression of miR-483-3p is strongly enhanced in pancreatic cancer tissues compared to side normal tissues using a miRNA-array differential analysis. Furthermore, DPC4/Smad4 is identified as a target of miR-483-3p and their expression levels are inversely correlated in human clinical specimens. Ectopic expression of miR-483-3p significantly represses DPC4/Smad4 protein levels in pancreatic cancer cell lines, and simultaneously promotes cell proliferation and colony formation in vitro. Our findings identify miR-483-3p as a potent regulator of DPC4/Smad4, which may provide a novel therapeutic strategy for the treatment of DPC4/Smad4-driven pancreatic cancer.

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    • "This study suggested that miR-494 might be developed as a prognostic marker or a therapeutic target for patients with PDAC. Other studies have shown that in human PDAC specimens, the expression levels of both miR-421 and miR-483-3p are inversely correlated to SMAD4 expression and ectopic expression of these miRNAs significantly represses SMAD4 protein levels in PDAC cell lines, suggesting that they are potent regulators of SMAD4 in PDAC [89, 90]. "
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    • "Ectopic expression of miR-421 decreased levels of DPC4/Smad4 protein, and promoted proliferation and colony formation in vitro, suggesting that miR-421 promotes oncogenesis by acting on DPC4/Smad4[46]. A similar study showed that up-regulated miR-483-3p also targets DPC4/Smad4 in PDAC tissues[47]. "
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    ABSTRACT: 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.
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