hnRNP A2/B1 modulates epithelial-mesenchymal transition in lung cancer cell lines.

Abstract

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) has been reported to be overexpressed in lung cancer and in other cancers such as breast, pancreas, and liver. However, a mechanism linking hnRNP A2/B1 overexpression and progression to cancer has not yet been definitively established. To elucidate this mechanism, we have silenced hnRNPA2/B1 mRNA in non-small-cell lung cancer cell lines A549, H1703, and H358. These cell lines present different levels of expression of epithelial-to-mesenchymal transition (EMT) markers such as E-cadherin, fibronectin, and vimentin. Microarray expression analysis was performed to evaluate the effect of silencing hnRNP A2/B1 in A549 cells. We identified a list of target genes, affected by silencing of hnRNP A2/B1, that are involved in regulation of migration, proliferation, survival, and apoptosis. Silencing hnRNP A2/B1 induced formation of cell clusters and increased proliferation. In the anchorage-independent assay, silencing hnRNP A2/B1 increased colony formation by 794% in A549 and 174% in H1703 compared with a 25% increase in proliferation, in both cell lines, in a two-dimensional proliferation assay. Silencing hnRNP A2/B1 decreased migration in intermediate cell line A549 and mesenchymal cell line H1703; however, no changes in proliferation were observed in epithelial cell line H358. Silencing hnRNP A2/B1 in A549 and H1703 cells correlated with an increase of E-cadherin expression and downregulation of the E-cadherin inhibitors Twist1 and Snai1. These data suggest that expression of hnRNP A2/B1 may play a role in EMT, in nonepithelial lung cancer cell lines A549 and H1703, through the regulation of E-cadherin expression.

• Authors: Jordi Tauler, Enrique Zudaire, Huaitian Liu, Joanna Shih, James L Mulshine
• Journal: Cancer research (Cancer Res) Vol. 70 Issue 18 Pg. 7137-47 (Sep 15 2010) ISSN: 1538-7445 [Electronic] United States
• PMID: 20807810 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: ©2010 AACR.

Chemical References

• Cadherins
• Heterogeneous-Nuclear Ribonucleoprotein Group A-B
• Nuclear Proteins
• SNAI1 protein, human
• Snail Family Transcription Factors
• TWIST1 protein, human
• Transcription Factors
• Twist-Related Protein 1

Topics

• Cadherins (antagonists & inhibitors)
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology)
• Cell Growth Processes (physiology)
• Cell Line, Tumor
• Cell Movement (physiology)
• Epithelial Cells (pathology)
• Gene Silencing
• Heterogeneous-Nuclear Ribonucleoprotein Group A-B (biosynthesis, genetics)
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• Mesoderm (pathology)
• Nuclear Proteins (biosynthesis)
• Snail Family Transcription Factors
• Transcription Factors (biosynthesis)
• Twist-Related Protein 1 (biosynthesis)