MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene

Lu, Zhongxin; Liu, M.; Stribinskis, Vilius; Klinge, Carolyn M.; Ramos, K. S.; Colburn, Nancy H.; Li, Yong

doi:10.1038/onc.2008.72

Cited by 635 publications

(473 citation statements)

References 38 publications

(63 reference statements)

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“…In colorectal cells, the level of miR-21 and Pdcd4 expression were shown to have an inverse correlation. A luciferase construct showed down-regulation of the PDCD4 promoter activity upon overexpression of miR-21, which is due to the direct targeting of the 3′UTR[16]. pdcd4 inhibition by miR-21 causes an increased invasion in colorectal cells[17].…”

Section: Mir-21 Targetsmentioning

confidence: 96%

Apoptosis and the target genes of microRNA-21

Buscaglia¹,

Yong²

2011

Chin J Cancer

214

180

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MicroRNA-21 (miR-21) is frequently up-regulated in cancer and the majority of its reported targets are tumor suppressors. Through functional suppression, miR-21 is implicated in practically every walk of oncogenic life: the promotion of cell proliferation, invasion and metastasis, genome instability and mutation, inflammation, replicative immortalization, abnormal metabolism, angiogenesis, and evading apoptosis, immune destruction, and growth suppressors. In particular, miR-21 is strongly involved in apoptosis. In this article, we reviewed the experimentally validated targets of miR-21 and found that two thirds are linked to intrinsic and/or extrinsic pathways of cellular apoptosis. This suggests that miR-21 is an Oncogene which plays a key role in resisting programmed cell death in cancer cells and that targeting apoptosis is a viable therapeutic option against cancers expressing miR-21.

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Section: Mir-21 Targetsmentioning

confidence: 96%

Apoptosis and the target genes of microRNA-21

Buscaglia¹,

Yong²

2011

Chin J Cancer

214

180

View full text Add to dashboard Cite

show abstract

“…For instance, miR-21 has been shown to be overexpressed in a variety of cancers and targets phosphatase and tensin homolog (PTEN), reversion-inducingcysteine-rich protein with kazal motifs (RECK), programmed cell death and four other genes as well as tropomyosin-1 (Meng et al, 2006;Si et al, 2007;Zhu et al, 2007;Lu et al, 2008;Zhang et al, 2008). In contrast, let-7 is a tumor-suppressive miRNA family and is underexpressed in various tumors; it targets Ras, HMGA2 and others genes (Johnson et al, 2005;Yanaihara et al, 2006;Motoyama et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of miR-370 and downregulation of its novel target TGFβ-RII contribute to the progression of gastric carcinoma

et al. 2011

Oncogene

101

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MicroRNAs (miRNAs) are endogenous non-coding RNAs that are known to be involved in the pathogenesis of tumors. Gastric carcinoma (GC) is a common malignancy worldwide. The aim of this study was the identification of the expression signature and functional roles of aberrant miRNAs in GC. Initial screening established a profile of aberrantly expressed miRNAs in tumors. miR-370 was confirmed to be overexpressed in GC tissues. Higher expression of miR-370 in GC tissues was associated with more advanced nodal metastasis and a higher clinical stage compared with controls. In addition, significantly higher level of miR-370 was noted in the plasma of GC patients compared with controls. Patients having more invasive or advanced tumors also exhibited a higher plasma level of miR-370. In vitro assays indicated that exogenous miR-370 expression enhanced the oncogenic potential of GC cells. The AGS-GFPM2 cells with exogenous miR-370 expression also exhibited enhanced abdominal metastatic dissemination in nude mice. Reporter assays confirmed that miR-370 targeted predicted sites in 3 0 UTR of transforming growth factor-b receptor II (TGFb-RII) gene. The exogenous miR-370 expression decreased TGFb-RII expression and the phosphorylation of Smad3 elicited by TGFb1. The TGFb1-mediated repression in cell migration was reverted by exogenous miR-370 expression. A reverse correlation between miR-370 and TGFb-RII expression was noted in GC tissues. This study concludes that miR-370 is a miRNA that is associated with GC progression by downregulating TGFb-RII. The miRNA expression profile described in this study should contribute to future studies on the role of miRNAs in GC.

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“…Pdcd4 expression is controlled by multiple mechanisms. Pdcd4 mRNA is targeted by microRNA miR-21, whose overexpression in cancer cells downregulates Pdcd4 expression (Asangani et al, 2008;Lu et al, 2008). On the protein level, p70(S6K) kinase-mediated phosphorylation of Pdcd4 triggers its ubiquitinylation by the E3 ubiquitin ligase complex SCF(betaTRCP) and its subsequent degradation (Dorello et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Pdcd4 directly binds the coding region of c-myb mRNA and suppresses its translation

et al. 2011

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Pdcd4 is a novel tumor suppressor protein that functions in the nucleus and the cytoplasm, and appears to be involved in the regulation of transcription and translation. In the cytoplasm, Pdcd4 has been implicated in the suppression of translation of mRNAs containing structured 5 0 -untranslated regions; however, the mechanisms that recruit Pdcd4 to specific target mRNAs and the identities of these mRNAs are mostly unknown. In this study, we have identified c-myb mRNA as the first natural translational target mRNA of Pdcd4. We have found that translational suppression of c-myb mRNA by Pdcd4 is dependent on sequences located within the c-myb-coding region. Furthermore, we have found that the N-terminal domain of Pdcd4 has an important role in targeting Pdcd4 to c-myb RNA by mediating preferential RNA binding to the Pdcd4-responsive region of c-myb mRNA. Overall, our work demonstrates for the first time that Pdcd4 is directly involved in translational suppression of a natural mRNA and provides the first evidence for a key role of the RNA-binding domain in targeting Pdcd4 to a specific mRNA.

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MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene

Cited by 635 publications

References 38 publications

Apoptosis and the target genes of microRNA-21

Apoptosis and the target genes of microRNA-21

Overexpression of miR-370 and downregulation of its novel target TGFβ-RII contribute to the progression of gastric carcinoma

Pdcd4 directly binds the coding region of c-myb mRNA and suppresses its translation

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