The galanin signaling cascade is a candidate pathway regulating oncogenesis in human squamous cell carcinoma

Abstract

To identify putative biomarkers in squamous cell carcinoma (SCC), a survey of parallel chromosomal alterations and gene expression studies in 10 SCC cell lines were performed using array-comparative genomic hybridization (CGH) and oligo-microarray techniques. The most frequent changes were gains of 11q13.1-13.3 and losses of 18q12.1-23 in SCC. Furthermore, the expression levels of the sets of genes at both these loci in SCC were measured using microarray analysis. By combining the array-CGH with the microarray data, 10 genes at 11q13.1-13.3 and 6 genes at 18q12.1-23 whose expression correlated with chromosomal alterations were identified. To verify the expression levels of the identified genes, we used expression analysis data derived from our earlier study of clinical specimens. In clinical samples, six genes (GAL, GSTP1, MRPL11, MRPL21, SF3B2, and YIF1A) at 11q13.1-13.3 and one gene (GALR1) at 18q23 showed a significant difference between normal and tumor samples. GAL, coding for the neuropeptide galanin, and GALR1, a galanin receptor, were identified as candidate genes of oncogenesis in SCC. The expression levels of GAL, GALR1, GALR2, and GALR3 were confirmed by real-time PCR. The expression ratio between GAL and GALR1 showed a significant negative correlation. GALR1 is a G-protein-coupled receptor that activates GTP-binding proteins to trigger signaling cascades such as the mitogen-activated protein kinase pathway, and is a well-established mitogenic pathway. This further supports the hypothesis that the genes involved in the GAL signaling cascade are candidates for regulation of oncogenesis in SCC.

Tumor suppressive microRNA-133a regulates novel molecular networks in lung squamous cell carcinoma

“…Hybridization and wash steps were performed as previously described. 19 The arrays were scanned using a Packard GSI Lumonics ScanArray 4000 (Perkin Elmer, Boston, MA, USA). The data were analyzed by means of DNASIS array software (Hitachi Software Engineering, Tokyo, Japan), which converted the signal intensity for each spot into text format.…”

“…Data from each microarray study were normalized by a global normalization method. 19 Predicted target genes and their miRNA binding site seed regions were investigated using TargetScan (release 5.1, http://www.targetscan.org/). The sequences of the predicted mature miRNAs were confirmed using miRBase (release 17.0, http://microrna.sanger.ac.uk/).…”

“…Recent studies have revealed that the normal regulatory mechanisms in these cancer pathways are disrupted by aberrant expression of microRNA (miRNA). 8 MiRNAs are a class of small non-coding RNA molecules consisting of [19][20][21][22] nucleotides that regulate gene expression through translational repression and mRNA cleavage, 8 and have an important role in a variety of biological processes, including development, differentiation, apoptosis and cell proliferation. Bioinformatic predictions indicate that miRNAs regulate more than 30% of protein coding genes.…”

Tumor suppressive microRNA-375 regulates oncogene AEG-1/MTDH in head and neck squamous cell carcinoma (HNSCC)

“…Hybridization and wash steps were performed as previously described. 22 The arrays were scanned using a Packard GSI Lumonics ScanArray 4000 (Perkin Elmer, Boston, MA, USA). The data were analyzed by means of DNASIS array software (Hitachi Software Engineering, Tokyo, Japan), which converted the signal intensity for each spot into text format.…”

“…Data from each microarray study were normalized by a global normalization method. 22 Predicted target genes and their target miRNA-binding site seed regions were investigated using TargetScan (release 5.1, http://www.targetscan.org/). The sequences of the predicted mature miRNAs were confirmed using miRBase (release 17.0, http://microrna.sanger.ac.uk/).…”