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      E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer.

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          Abstract

          Deregulation of E2F1 activity and resistance to TGFbeta are hallmarks of gastric cancer. MicroRNAs (miRNAs) are small noncoding RNAs frequently misregulated in human malignancies. Here we provide evidence that the miR-106b-25 cluster, upregulated in a subset of human gastric tumors, is activated by E2F1 in parallel with its host gene, Mcm7. In turn, miR-106b and miR-93 regulate E2F1 expression, establishing a miRNA-directed negative feedback loop. Furthermore, upregulation of these miRNAs impairs the TGFbeta tumor suppressor pathway, interfering with the expression of CDKN1A (p21(Waf1/Cip1)) and BCL2L11 (Bim). Together, these results suggest that the miR-106b-25 cluster is involved in E2F1 posttranscriptional regulation and may play a key role in the development of TGFbeta resistance in gastric cancer.

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          Author and article information

          Journal
          Cancer Cell
          Cancer cell
          Elsevier BV
          1878-3686
          1535-6108
          Mar 2008
          : 13
          : 3
          Affiliations
          [1 ] Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Ohio State University, 460 West 12th Avenue, Columbus, OH 43210, USA.
          Article
          S1535-6108(08)00049-4
          10.1016/j.ccr.2008.02.013
          18328430
          b446ff5f-a4db-40c6-b58a-ac972fd36266
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