nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.04.2012 | Original Article

PDCD4 expression inversely correlated with miR-21 levels in gastric cancers

verfasst von: Zhang Cao, Jung Hwan Yoon, Suk Woo Nam, Jung Young Lee, Won Sang Park

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 4/2012

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The specific aim of this study was to investigate whether the PDCD4 gene is involved in the development and progression of gastric cancer.

Methods

We examined the genetic and epigenetic alterations of the PDCD4 gene as well as the expression of PDCD4 protein in gastric cancers. The mRNA expression of PDCD4 and miRNA-21 expression were also analyzed using quantitative real-time RT-PCR.

Results

Loss or reduced PDCD4 expression was observed in 79 (36.7%) of 215 gastric cancer specimens. Statistically, altered PDCD4 expression was not associated with the clinicopathological parameters, including tumor differentiation, location, lymph node metastasis and overall survival (P > 0.05). miRNA-21 overexpression was frequently detected in gastric cancers (31 of 46, 67.4%), and there was a significant inverse correlation between miRNA-21 and PDCD4 protein expression (P = 0.029), but not between miRNA-21 and PDCD4 mRNA expression. In genetic analysis, no mutation was detected in the coding region of the PDCD4 gene, and promoter hypermethylation was found in 24 (36.4%) of the 66 gastric cancer samples.

Conclusions

Our data suggest that overexpression of miRNA-21 and reduced or loss of PDCD4 expression may play a role in the development and progression of gastric cancers.

Allgayer H (2010) Pdcd4, a colon cancer prognostic that is regulated by a microRNA. Crit Rev Oncol Hematol 73:185–191PubMedCrossRef

Asangani IA, Rasheed SA, Nikolova DA et al (2008) MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27:2128–2136PubMedCrossRef

Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6:857–866PubMedCrossRef

Calin GA, Dumitru CD, Shimizu M et al (2002) Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 99:15524–15529PubMedCrossRef

Chen Y, Knösel T, Kristiansen G et al (2003) Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis. J Pathol 200:640–646PubMedCrossRef

Chen C, Ridzon DA, Broomer AJ et al (2005) Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 33:e179PubMedCrossRef

Esquela-Kerscher A, Slack FJ (2006) Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer 6:259–269PubMedCrossRef

Frankel LB, Christoffersen NR, Jacobsen A et al (2008) Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem 283:1026–1033PubMedCrossRef

Gao F, Wang X, Zhu F et al (2009) PDCD4 gene silencing in gliomas is associated with 5′CpG island methylation and unfavorable prognosis. J Cell Mol Med 13:4257–4267PubMedCrossRef

Goke R, Barth P, Schmidt A et al (2004) Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21(Waf1/Cip1). Am J Physiol Cell Physiol 287:C1541–C1546PubMedCrossRef

Grunau C, Clark SJ, Rosenthal A (2001) Bisulfite genomic sequencing: systematic investigation of critical experimental parameters. Nucleic Acids Res 29:E65–E75PubMedCrossRef

Hiyoshi Y, Kamohara H, Karashima R et al (2009) MicroRNA-21 regulates the proliferation and invasion in esophageal squamous cell carcinoma. Clin Cancer Res 15:1915–1922PubMedCrossRef

Johnson SM, Grosshans H, Shingara J et al (2005) RAS is regulated by the let-7 microRNA family. Cell 120:635–647PubMedCrossRef

Kononen J, Bubendorf L, Kallioniemi A et al (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4:844–847PubMedCrossRef

Kusenda B, Mraz M, Mayer J et al (2006) MicroRNA biogenesis, functionality, and cancer relevance. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 150:205–215PubMed

Lee JY, Dong SM, Kim SY et al (1998) A simple, precise and economical microdissection technique for analysis of genomic DNA from archival tissue sections. Virchows Arch 433:305–309PubMedCrossRef

Lehmann U, Hasemeier B, Lilischkis R et al (2001) Quantitative analysis of promoter hypermethylation in laser-microdissected archival specimens. Lab Invest 81:635–638PubMedCrossRef

Ma L, Teruya-Feldstein J, Weinberg RA (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449:682–688PubMedCrossRef

Meng F, Henson R, Wehbe-Janek H et al (2007) MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133:647–658PubMedCrossRef

Motoyama K, Inoue H, Mimori K et al (2010) Clinicopathological and prognostic significance of PDCD4 and microRNA-21 in human gastric cancer. Int J Oncol 36:1089–1095PubMed

Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45PubMedCrossRef

Scott GK, Mattie MD, Berger CE et al (2006) Rapid alteration of microRNA levels by histone deacetylase inhibition. Cancer Res 66:1277–1281PubMedCrossRef

Shenouda SK, Alahari SK (2009) MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev 28:369–378PubMedCrossRef

Shibahara K, Asano M, Ishida Y et al (1995) Isolation of a novel mouse gene MA-3 that is induced upon programmed cell death. Gene 215:297–301CrossRef

Shin HR, Jung KM, Won YJ et al (2004) 2002 Annual report of the Korea central cancer registry: based on registered data from 139 hospitals. Cancer Res Treat 36:103–114PubMedCrossRef

Si ML, Zhu S, Wu H et al (2007) miR-21-mediated tumor growth. Oncogene 26:2799–2803PubMedCrossRef

Soejima H, Miyoshi O, Yoshinaga H et al (1999) Assignment of the programmed cell death 4 gene (PDCD4) to human chromosome band 10q24 by in situ hybridization. Cytogenet Cell Genet 87:113–114PubMedCrossRef

Takamizawa J, Konishi H, Yanagisawa K et al (2004) Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64:3753–3756PubMedCrossRef

Tili E, Michaille JJ, Alder H et al (2010) Resveratrol modulates the levels of microRNAs targeting genes encoding tumor-suppressors and effectors of TGFβ signaling pathway in SW480 cells. Biochem Pharmacol 12:2057–2065CrossRef

Wang Q, Sun ZX, Allgayer H et al (2010) Downregulation of E-cadherin is an essential event in activating beta-catenin/Tcf-dependent transcription and expression of its target genes in Pdcd4 knockdown cells. Oncogene 29:128–138PubMedCrossRef

Wei NA, Liu SS, Leung TH et al (2009) Loss of Programmed cell death 4 (Pdcd4) associates with the progression of ovarian cancer. Mol Cancer 8:70PubMedCrossRef

Wen YH, Shi X, Chiriboga L et al (2007) Alterations in the expression of PDCD4 in ductal carcinoma of the breast. Oncol Rep 18:1387–1393PubMed

Werner M, Becker KF, Keller G et al (2001) Gastric adenocarcinoma: pathomorphology and molecular pathology. J Cancer Res Clin Oncol 127:207–216PubMedCrossRef

Yang HS, Jansen AP, Nair R et al (2001) A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-kappaB or ODC transactivation. Oncogene 20:669–676PubMedCrossRef

Yoon JH, Song JW, Zhang C et al (2011) Inactivation of the Gastrokine 1 gene in gastric adenomas and carcinomas. J Pathol 223:618–625PubMedCrossRef

Zamore PD, Haley B (2005) Ribo-gnome: the big world of small RNAs. Science 309:1519–1524PubMedCrossRef

Zhang Z, Li Z, Gao C et al (2008) miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Lab Invest 88:1358–1366PubMedCrossRef

Zhu S, Si ML, Wu H et al (2007) MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 282:14328–14336PubMedCrossRef

Zhu S, Wu H, Wu F et al (2008) Micro-RNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res 18:350–359PubMedCrossRef

Titel: PDCD4 expression inversely correlated with miR-21 levels in gastric cancers
verfasst von: Zhang Cao
Jung Hwan Yoon
Suk Woo Nam
Jung Young Lee
Won Sang Park
Publikationsdatum: 01.04.2012
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 4/2012
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-011-1140-8

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

PDCD4 expression inversely correlated with miR-21 levels in gastric cancers

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Onkologie

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

Alter verschlechtert Prognose bei Endometriumkarzinom

Darf man die Behandlung eines Neonazis ablehnen?

Erhöhte Mortalität bei postpartalem Brustkrebs

Update Onkologie

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2012

Overexpression of tumor suppressor TSLC1 by a survivin-regulated oncolytic adenovirus significantly inhibits hepatocellular carcinoma growth

Inducible expression of tissue factor in small-cell lung cancer: impact on morphology and matrix metalloproteinase secretion

MiR-181d acts as a tumor suppressor in glioma by targeting K-ras and Bcl-2

Expression of tumor suppressor gene ING4 in ovarian carcinoma is correlated with microvessel density

Racial disparities in treatment for pancreatic cancer and impact on survival: a population-based analysis

The functional MDM2 T309G genetic variant but not P53 Arg72Pro polymorphism is associated with risk of sarcomas: a meta-analysis

Neu im Fachgebiet Onkologie

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

Alter verschlechtert Prognose bei Endometriumkarzinom

Darf man die Behandlung eines Neonazis ablehnen?

Erhöhte Mortalität bei postpartalem Brustkrebs

Update Onkologie