Downstream targets of heterogeneous nuclear ribonucleoprotein A2 mediate cell proliferation

He, Yaowu, Rothnagel, Joseph A., Epis, Michael R., Leedman, Peter J. and Smith, Ross (2009) Downstream targets of heterogeneous nuclear ribonucleoprotein A2 mediate cell proliferation. Molecular Carcinogenesis, 48 2: 167-179. doi:10.1002/mc.20467


Author He, Yaowu
Rothnagel, Joseph A.
Epis, Michael R.
Leedman, Peter J.
Smith, Ross
Title Downstream targets of heterogeneous nuclear ribonucleoprotein A2 mediate cell proliferation
Journal name Molecular Carcinogenesis   Check publisher's open access policy
ISSN 1098-2744
0899-1987
Publication date 2009-08-04
Year available 2009
Sub-type Article (original research)
DOI 10.1002/mc.20467
Open Access Status Not yet assessed
Volume 48
Issue 2
Start page 167
End page 179
Total pages 13
Place of publication New York , U.S.A
Publisher John Wiley & Sons
Language eng
Subject C1
060199 Biochemistry and Cell Biology not elsewhere classified
970106 Expanding Knowledge in the Biological Sciences
Abstract Over-expression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is regarded as an early marker for several cancers. This protein is associated with proto-oncogenes and tumor suppressor genes and has itself been described as a proto-oncogene. Our earlier experiments drew a connection between hnRNP A2/B1 levels and cell proliferation and raised the possibility that this protein contributes to the uncontrolled cell division that characterizes cancer. Limited knowledge of the downstream targets of hnRNP A2/B1 has, however, precluded a clear understanding of their roles in cancer cell growth. To define the pathways in which this protein acts we have now carried out microarray experiments with total RNA from Colo16 epithelial cells transfected with an shRNA that markedly suppresses hnRNP A2/B1 expression. The microarray data identified 123 genes, among 22 283 human gene probe sets, with altered expression levels in hnRNP A2/B1-depleted cells. Ontological analysis showed that many of these downstream targets are involved in regulation of the cell cycle and cell proliferation and that this group of proteins is significantly over-represented amongst the affected proteins. The changes detected in the microarray experiments were confirmed by real-time PCR for a subset of proliferation-related genes. Immunoprecipitation-RT-PCR demonstrated that hnRNP A2/B1 formed complexes with the transcripts of many of the verified downstream genes, suggesting that hnRNP A2/B1 contributes to the regulation of these genes. These results reinforce the conclusion that hnRNP A2/B1 is associated with cellular processes that affect the cell cycle and proliferation. © 2008 Wiley-Liss, Inc.
Keyword cancer
small interfering RNA
HnRNP
immunoprecipitation
microarray
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Chemistry and Molecular Biosciences
 
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Created: Wed, 01 Apr 2009, 18:11:32 EST by Jennifer Falknau on behalf of School of Chemistry & Molecular Biosciences