The proto‐oncogene<scp>ERG</scp>is a target of micro<scp>RNA</scp><i>miR‐145</i>in prostate cancer

Hart, Martin; Wach, Sven; Nolte, Elke; Szczyrba, Jaroslaw; Menon, Roopika; Täubert, Helge; Hartmann, Arndt; Stoehr, Robert; Wieland, Wolf F.; Grässer, Friedrich A.; Wullich, Bernd

doi:10.1111/febs.12236

Cited by 58 publications

(35 citation statements)

References 40 publications

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“…There are as of now only few studies that demonstrate binding of a specific miRNA to members of a protein family. Recently, we reported binding of miR-145 to the proto-oncogene ERG (the v-ets avian erythroblastosis virus e26 oncogene homolog), which belongs to the large family of ETS (E26 transformation-specific) transcription factors [30]. The same miRNA also binds to FLI-1 (Friend leukemia virus integration 1) and ETS-1 (v-ets erythroblastosis virus E26 oncogene homolog 1), which are both members of the ETS family of transcription factors [31, 32].…”

Section: Discussionmentioning

confidence: 99%

“…The same miRNA also binds to FLI-1 (Friend leukemia virus integration 1) and ETS-1 (v-ets erythroblastosis virus E26 oncogene homolog 1), which are both members of the ETS family of transcription factors [31, 32]. We suggested that miR-145 might regulate different members of this transcription factor family towards suppression of cell growth [30]. With 29 genes belonging to the ETS family in humans, the hypothesis was, however, based only on circumstantial evidence.…”

Section: Discussionmentioning

confidence: 99%

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Identification of miR-34a-target interactions by a combined network based and experimental approach

et al. 2016

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Circulating miRNAs have been associated with numerous human diseases. The lack of understanding the functional roles of blood-born miRNAs limits, however, largely their value as disease marker. In a systems biology analysis we identified miR-34a as strongly associated with pathogenesis. Genome-wide analysis of miRNAs in blood cell fractions highlighted miR-34a as most significantly up-regulated in CD3+ cells of lung cancer patients. By our in silico analysis members of the protein kinase C family (PKC) were indicated as miR-34a target genes. Using a luciferase assay, we confirmed binding of miR-34a-5p to target sequences within the 3′UTRs of five PKC family members. To verify the biological effect, we transfected HEK 293T and Jurkat cells with miR-34a-5p causing reduced endogenous protein levels of PKC isozymes. By combining bioinformatics approaches with experimental validation, we demonstrate that one of the most relevant disease associated miRNAs has the ability to control the expression of a gene family.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of miR-34a-target interactions by a combined network based and experimental approach

et al. 2016

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“…miR-30 tumor suppressor has been demonstrated to connect the major EGF/Src signaling to ERG providing mechanistic insights into EMT features of ERG-positive CaP cells [21]. miR-145 has been shown to inhibit ERG expression by directly targeting its 3′-UTR [22]. Thus, loss of miR-145 may provide a TMPRSS2–ERG gene fusion-independent means to ERG up-regulation in CaP.…”

Section: Introductionmentioning

confidence: 99%

Loss of miR-449a in ERG-associated prostate cancer promotes the invasive phenotype by inducing SIRT1

et al. 2016

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Epigenetic regulation by SIRT1, a multifaceted NAD+-dependent protein deacetylase, is one of the most common factors modulating cellular processes in a broad range of diseases, including prostate cancer (CaP). SIRT1 is over-expressed in CaP cells, however the associated mechanism is not well understood. To identify whether specific microRNAs might mediate this linkage, we have screened a miRNA library for differential expression in ERG-associated CaP tissues. Of 20 differentially and significantly expressed miRNAs that distinguish ERG-positive tumors from ERG-negative tumors, we find miR-449a is highly suppressed in ERG-positive tumors. We establish that SIRT1 is a direct target of miR-449a and is also induced by ERG in ERG-associated CaP. Our data suggest that attenuation of miR-449a promotes the invasive phenotype of the ERG-positive CaP in part by inducing the expression of SIRT1 in prostate cancer cells. Furthermore, we also find that suppression of SIRT1 results in a significant reduction in ERG expression in ERG-positive CaP cells, indicating a feed-back regulatory loop associated with ERG, miR-449a and SIRT1. We also report that ERG suppresses p53 acetylation perhaps through miR-449a-SIRT1 axis in CaP cells. Our findings provide new insight into the function of miRNAs in regulating ERG-associated CaP. Thus, miR-449a activation or SIRT1 suppression may represent new therapeutic opportunity for ERG-associated CaP.

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“…Overexpression in prostate cancer (PCa)-derived LNCaP cells promotes proliferation and a dramatic increase in colony formation [24,25]. Many miRs function as oncogenes or tumor suppressors in human cancers [26][27][28][29][30][31][32]. Downregulation of miR-145 has been reported in PCa, suggesting that miR-145 functions as a tumor suppressor [33].…”

Section: Introductionmentioning

confidence: 99%

Reciprocal regulation of PCGEM1 and miR-145 promote proliferation of LNCaP prostate cancer cells

Zhang

Han

et al. 2014

J Exp Clin Cancer Res

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Prostate cancer gene expression marker 1 (PCGEM1) is a long non-coding RNA (lncRNA) overexpressed in prostate cancer (PCa) cells that promotes PCa initiation and progression, and protects against chemotherapy-induced apoptosis. The microRNA miR-145 functions as a tumor suppressor in PCa. We speculate that reciprocal regulation of PCGEM1 and miR-145 promote proliferation of LNCaP prostate cancer cells. To test this hypothesis, the interaction between PCGEM1 and miR-145 was examined using a luciferase reporter assay. Expression levels were selectively altered in LNCaP cells and noncancerous RWPE-1 prostate cells by transfection of miR-145 or small interfering RNA sequences against (siRNA) PCGEM1. Relative expression levels were detected by RT-PCR, tumor cell growth and early apoptosis by the MTT assay and flow cytometry, respectively, and tumor cell migration and invasion properties by transwell assays. The effect of siRNA PCGEM1 and miR-145 transfection on prostate cancer growth in vivo was examined in the (nu/nu) mouse model. PCGEM1 and miR-145 exhibited reciprocal regulation; downregulation of PCGEM1 expression in LNCaP cells increased expression of miR-145, while overexpression of miR-145 decreased PCGEM1 expression. Transfection of the miR-145 expression vector and siRNA PCGEM1 inhibited tumor cell proliferation, migration, and invasion, and induced early apoptosis both in vitro. In contrast, there was no effect on RWPE-1 cells. We demonstrate a reciprocal negative control relationship between PCGEM1 and miR-145 that regulates both LNCaP cell proliferation and nu/nu PCa tumor growth. The results also identify PCGEM1 and associated regulators as possible targets for PCa therapy.

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The proto‐oncogeneERGis a target of microRNAmiR‐145in prostate cancer

Cited by 58 publications

References 40 publications

Identification of miR-34a-target interactions by a combined network based and experimental approach

Identification of miR-34a-target interactions by a combined network based and experimental approach

Loss of miR-449a in ERG-associated prostate cancer promotes the invasive phenotype by inducing SIRT1

Reciprocal regulation of PCGEM1 and miR-145 promote proliferation of LNCaP prostate cancer cells

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