hnRNP A2/B1 modulates epithelial-mesenchymal transition in lung cancer cell lines.
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.
Tauler
Jordi
J
Laboratory of Lung Cancer Biology, Section of Medical Oncology, Rush University Medical Center, Chicago, Illinois 60612, USA. Jordi_Tauler@rush.edu
Zudaire
Enrique
E
Liu
Huaitian
H
Shih
Joanna
J
Mulshine
James L
JL
D015820:Cadherins / Q000037:antagonists & inhibitors; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D004847:Epithelial Cells / Q000473:pathology; D020868:Gene Silencing; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008648:Mesoderm / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis; D051879:Twist-Related Protein 1 / Q000096:biosynthesis
D015820:Cadherins; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D009687:Nuclear Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1