Human basonuclin 2 up-regulates a cascade set of interferon-stimulated genes with anti-cancerous properties in a lung cancer model.
BACKGROUND
Human basonuclin 2 (BNC2) acts as a tumor suppressor in multiple cancers in an as yet unidentified manner. The role and expression of theBNC2gene in lung cancer has not yet been investigated.


METHODS
BNC2 expression was studied in the A549 and BEAS-2B cell lines, as well as in lung cancer tissue. Illumina array analysis and a viability assay were used to study the effects of transient transfection of BNC2 in A549 cells. Ingenuity pathway analysis and g:Profiler were applied to identify affected pathways and networks. RT-qPCR was used to validate the array results.


RESULTS
We showed the reduced mRNA expression of BNC2 in non-small cell lung cancer tissue and lung cancer cell line A549 compared to non-cancerous lung tissue and BEAS-2B cells, respectively. Further array analysis demonstrated that the transfection of BNC2 into A549 cells resulted in the increased expression of 139 genes and the down-regulation of 13 genes. Pathway analysis revealed that half of the up-regulated genes were from the interferon/signal transducer and activator of transcription signaling pathways. The differential expression of selected sets of genes, including interferon-stimulated and tumor suppressor genes of theXAF1andOASfamilies, was confirmed by RT-qPCR. In addition, we showed that the over-expression of BNC2 inhibited the proliferation of A549 cells.


CONCLUSIONS
Our data suggest that human BNC2 is an activator of a subset of IFN-regulated genes and might thereby act as a tumor suppressor.
Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.|Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
Egon
E
Urgard
Estonian Genome Center, University of Tartu, Tartu, Estonia.
Anu
A
Reigo
Department of Immunoanalysis, United Laboratories, Tartu University Hospital, Tartu, Estonia.
Eva
E
Reinmaa
Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
Ana
A
Rebane
Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.|Estonian Genome Center, University of Tartu, Tartu, Estonia.
Andres
A
Metspalu
BNC2; Lung cancer; OAS family; Type I IFN; XAF1