skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Expression of programmed cell death protein 4 (PDCD4) and miR-21 in urothelial carcinoma

Abstract

Highlights: Black-Right-Pointing-Pointer The tumor suppressor gene PDCD4 is down-regulated in many tumorous entities. Black-Right-Pointing-Pointer We investigate the impact of PDCD4 and its regulating factor miR-21 in urothelial carcinoma. Black-Right-Pointing-Pointer We confirm PDCD4 as a tumor suppressor gene and it could be a diagnostic marker for this tumor. -- Abstract: Background: We investigated the role of the programmed cell death 4 (PDCD4) tumor suppressor gene in specimens of transitional cell carcinoma and of healthy individuals. Methods: PDCD4 immunohistochemical expression was investigated in 294 cases in histologically proven transitional cell carcinoma in different tumorous stages (28 controls, 122 non-muscle invasive urothelial carcinoma, stages Tis-T1, 119 invasive transitional cell carcinoma stages T2-T4 and 25 metastases). MiR-21 expression, an important PDCD4 regulator, was assessed with real-time PCR analysis and showed inverse correlation to tissue PDCD4 expression. Results: Nuclear and cytoplasmatic PDCD4 immunostaining decreased significantly with histopathological progression of the tumor (p < 0001). Controls showed strong nuclear and cytoplasmatic immunohistochemical staining. MiR-21 up regulation in tissue corresponded to PDCD4 suppression. Conclusions: These data support a decisive role for PDCD4 down regulation in transitional cell carcinoma and confirm miR-21 as a negative regulator for PDCD4. Additionally, PDCD4 immunohistochemical staining turns out to be a possiblemore » diagnostic marker for transitional cell carcinoma.« less

Authors:
 [1];  [2];  [1];  [3];  [1];  [1]
  1. Department of Urology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany)
  2. Department of Pathology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany)
  3. Department of Internal Medicine, Philipps-University of Marburg, Baldingerstrasse, 35043 Marburg (Germany)
Publication Date:
OSTI Identifier:
22207617
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 417; Journal Issue: 1; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; APOPTOSIS; BLADDER; CARCINOMAS; GENE REGULATION; GENES; INHIBITION; METASTASES; MUSCLES; POLYMERASE CHAIN REACTION; PROTEINS

Citation Formats

Fischer, Nicolas, E-mail: simplissimus@gmx.de, Goeke, Friederike, E-mail: Friederike.goeke@ukb.uni-bonn.de, Splittstoesser, Vera, E-mail: Veri.sp@web.de, Lankat-Buttgereit, Brigitte, E-mail: Lankatbu@staff.uni-marburg.de, Mueller, Stefan C., E-mail: Stefan.mueller@ukb.uni-bonn.de, and Ellinger, Joerg, E-mail: Joerg.ellinger@ukb.uni-bonn.de. Expression of programmed cell death protein 4 (PDCD4) and miR-21 in urothelial carcinoma. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2011.11.035.
Fischer, Nicolas, E-mail: simplissimus@gmx.de, Goeke, Friederike, E-mail: Friederike.goeke@ukb.uni-bonn.de, Splittstoesser, Vera, E-mail: Veri.sp@web.de, Lankat-Buttgereit, Brigitte, E-mail: Lankatbu@staff.uni-marburg.de, Mueller, Stefan C., E-mail: Stefan.mueller@ukb.uni-bonn.de, & Ellinger, Joerg, E-mail: Joerg.ellinger@ukb.uni-bonn.de. Expression of programmed cell death protein 4 (PDCD4) and miR-21 in urothelial carcinoma. United States. doi:10.1016/J.BBRC.2011.11.035.
Fischer, Nicolas, E-mail: simplissimus@gmx.de, Goeke, Friederike, E-mail: Friederike.goeke@ukb.uni-bonn.de, Splittstoesser, Vera, E-mail: Veri.sp@web.de, Lankat-Buttgereit, Brigitte, E-mail: Lankatbu@staff.uni-marburg.de, Mueller, Stefan C., E-mail: Stefan.mueller@ukb.uni-bonn.de, and Ellinger, Joerg, E-mail: Joerg.ellinger@ukb.uni-bonn.de. Fri . "Expression of programmed cell death protein 4 (PDCD4) and miR-21 in urothelial carcinoma". United States. doi:10.1016/J.BBRC.2011.11.035.
@article{osti_22207617,
title = {Expression of programmed cell death protein 4 (PDCD4) and miR-21 in urothelial carcinoma},
author = {Fischer, Nicolas, E-mail: simplissimus@gmx.de and Goeke, Friederike, E-mail: Friederike.goeke@ukb.uni-bonn.de and Splittstoesser, Vera, E-mail: Veri.sp@web.de and Lankat-Buttgereit, Brigitte, E-mail: Lankatbu@staff.uni-marburg.de and Mueller, Stefan C., E-mail: Stefan.mueller@ukb.uni-bonn.de and Ellinger, Joerg, E-mail: Joerg.ellinger@ukb.uni-bonn.de},
abstractNote = {Highlights: Black-Right-Pointing-Pointer The tumor suppressor gene PDCD4 is down-regulated in many tumorous entities. Black-Right-Pointing-Pointer We investigate the impact of PDCD4 and its regulating factor miR-21 in urothelial carcinoma. Black-Right-Pointing-Pointer We confirm PDCD4 as a tumor suppressor gene and it could be a diagnostic marker for this tumor. -- Abstract: Background: We investigated the role of the programmed cell death 4 (PDCD4) tumor suppressor gene in specimens of transitional cell carcinoma and of healthy individuals. Methods: PDCD4 immunohistochemical expression was investigated in 294 cases in histologically proven transitional cell carcinoma in different tumorous stages (28 controls, 122 non-muscle invasive urothelial carcinoma, stages Tis-T1, 119 invasive transitional cell carcinoma stages T2-T4 and 25 metastases). MiR-21 expression, an important PDCD4 regulator, was assessed with real-time PCR analysis and showed inverse correlation to tissue PDCD4 expression. Results: Nuclear and cytoplasmatic PDCD4 immunostaining decreased significantly with histopathological progression of the tumor (p < 0001). Controls showed strong nuclear and cytoplasmatic immunohistochemical staining. MiR-21 up regulation in tissue corresponded to PDCD4 suppression. Conclusions: These data support a decisive role for PDCD4 down regulation in transitional cell carcinoma and confirm miR-21 as a negative regulator for PDCD4. Additionally, PDCD4 immunohistochemical staining turns out to be a possible diagnostic marker for transitional cell carcinoma.},
doi = {10.1016/J.BBRC.2011.11.035},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 417,
place = {United States},
year = {Fri Jan 06 00:00:00 EST 2012},
month = {Fri Jan 06 00:00:00 EST 2012}
}
  • MicroRNAs are involved in cancer-related processes. The microRNA-21(miR-21) has been identified as the only miRNA over-expressed in a wide variety of cancers, including cervical cancer. However, the function of miR-21 is unknown in cervical carcinomas. In this study, we found that the inhibition of miR-21 in HeLa cervical cancer cells caused profound suppression of cell proliferation, and up-regulated the expression of the tumor suppressor gene PDCD4. We also provide direct evidence that PDCD4-3'UTR is a functional target of miR-21 and that the 18 bp putative target site can function as the sole regulatory element in HeLa cells. These results suggestmore » that miR-21 may play an oncogenic role in the cellular processes of cervical cancer and may serve as a target for effective therapies.« less
  • Highlights: •The oncogenic miR-17-5p is downregulated in non-metastatic hepatocellular carcinoma patients. •E2F-1 and c-MYC transcripts are upregulated in non-metastatic HCC patients. •miR-17-5p forced overexpression inhibited E2F-1 and c-MYC expression in HuH-7 cells. •miR-17-5p mimicking increased HuH-7 cell growth, proliferation, migration and colony formation. •miR-17-5p is responsible for HCC progression among the c-MYC/E2F-1/miR-17-5p triad members. -- Abstract: E2F-1, c-MYC, and miR-17-5p is a triad of two regulatory loops: a negative and a positive loop, where c-MYC induces the expression of E2F-1 that induces the expression of miR-17-5p which in turn reverses the expression of E2F-1 to close the loop. In thismore » study, we investigated this triad for the first time in hepatocellular carcinoma (HCC), where miR-17-5p showed a significant down-regulation in 23 non-metastatic HCC biopsies compared to 10 healthy tissues; however, E2F-1 and c-MYC transcripts were markedly elevated. Forced over-expression of miR-17-5p in HuH-7 cells resulted in enhanced cell proliferation, growth, migration and clonogenicity with concomitant inhibition of E2F-1 and c-MYC transcripts expressions, while antagomirs of miR-17-5p reversed these events. In conclusion, this study revealed a unique pattern of expression for miR-17-5p in non-metastatic HCC patients in contrast to metastatic HCC patients. In addition we show that miR-17-5p is the key player among the triad that tumor growth and spread.« less
  • Highlights: • miR-9 expression level was significantly decreased in OSCC tissues. • Curcumin significantly inhibited SCC-9 cells proliferation. • miR-9 mediates the inhibition of SCC-9 proliferation by curcumin. • Curcumin suppresses Wnt/β-catenin signaling in SCC-9 cells. • miR-9 mediates the suppression of Wnt/β-catenin signaling by curcumin. - Abstract: Curcumin, a phytochemical derived from the rhizome of Curcuma longa, has shown anticancer effects against a variety of tumors. In the present study, we investigated the effects of curcumin on the miR-9 expression in oral squamous cell carcinoma (OSCC) and explored the potential relationships between miR-9 and Wnt/β-catenin pathway in curcumin-mediated OSCCmore » inhibition in vitro. As the results shown, the expression levels of miR-9 were significantly lower in clinical OSCC specimens than those in the adjacent non-tumor tissues. Furthermore, our results indicated that curcumin inhibited OSCC cells (SCC-9 cells) proliferation through up-regulating miR-9 expression, and suppressing Wnt/β-catenin signaling by increasing the expression levels of the GSK-3β, phosphorylated GSK-3β and β-catenin, and decreasing the cyclin D1 level. Additionally, the up-regulation of miR-9 by curcumin in SCC-9 cells was significantly inhibited by delivering anti-miR-9 but not control oligonucleotides. Downregulation of miR-9 by anti-miR-9 not only attenuated the growth-suppressive effects of curcumin on SCC-9 cells, but also re-activated Wnt/β-catenin signaling that was inhibited by curcumin. Therefore, our findings would provide a new insight into the use of curcumin against OSCC in future.« less
  • MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at post-transcriptional level. miRNA dysregulation plays a causal role in cancer progression. In this study, miR-208-3p was highly expressed and directly repressed ARID2 expression. As a result, ARID2 expression in hepatocellular carcinoma (HCC) was decreased. In vitro, miR-208-3p down-regulation and ARID2 over-expression elicited similar inhibitory effects on HCC cell proliferation and invasion. In vivo test results revealed that miR-208-3p down-regulation inhibited HCC tumorigenesis in Hep3B cells. Moreover, ARID2 was possibly a downstream element of transforming growth factor beta1 (TGFβ1)/miR-208-3p/ARID2 regulatory pathway. These findings suggested that miR-208-3p up-regulation is associatedmore » with HCC cell progression and may provide a new target for liver cancer treatment. - Highlights: • miR-208-3p was highly expressed and directly repressed the expression of ARID2 in HCC. • miR-208-3p contributed to HCC cell progression both in vitro and in vivo. • Over-expression of ARID2 inhibited the HCC cell proliferation and invasion. • Restoration of ARID2 partly reversed the the effect of miR-208-3p down-regulation on HCC cells. • Newly regulatory pathway: miR-208-3p mediated the repression of ARID2 by TGFβ1 in HCC cells.« less