NAV3 copy number changes and target genes in basal and squamous cell cancers

Abstract

The neuron navigator 3 (NAV3) gene on chromosome 12q21 encodes a microtubule plus end tracking protein and belongs to the navigator family of cytoskeletal regulators. Loss of heterozygosity on 12q has previously been suggested to be associated with poor prognosis in cancers of epithelial origin. In this study, we characterized copy number changes of NAV3 in 24 basal cell cancers (BCCs), eight squamous cell cancers (SCCs) and eight non-malignant inflammatory skin lesions by fluorescent in situ hybridization. To identify genes affected by NAV3, we used oligo siRNA gene silencing and gene microarrays to analyse gene expression profiles at several time points post-transfection in primary human keratinocytes. We found NAV3 copy number loss and decreased protein expression in 21% of the BCCs and 25% of the SCCs. In the nodular/superficial BCC subgroup, low-level NAV3 amplification was also observed. NAV3 aberrations were independent of the known chromosome 6 amplifications in BCC. Chromosome 12 polysomy was detected in 33% and 25% of the invasive type of BCC and SCC, respectively. Silencing of NAV3 in primary human keratinocytes revealed 22 differentially expressed genes, mostly related to inflammation. The most relevant of these were validated with qPCR or immunohistochemistry. This pilot study suggests that NAV3 is a novel cancer-associated gene that contributes to the pathogenesis of a subgroup of BCC and SCC.

MiR-21 promoted proliferation and migration in hepatocellular carcinoma through negative regulation of Navigator-3

“…Navigator-3 (NAV-3) was first reported as a novel cancer-associated gene that leads to the pathogenesis of the basal and squamous cell cancers [9]. In breast cancer, Cohen-Dvashi H et al proposed that NAV-3 inhibited breast cancer progression by regulating microtubule dynamics, playing a metastasis-suppressing role [11].…”

“…The underlying mechanism by which miR-21 promotes metastasis, however, remains unknown. Navigator-3 (NAV-3) was first found and mentioned as a novel cancer-associated gene that contributes to the pathogenesis of the basal and squamous cell cancers [9]. Silencing of NAV-3 leads to the variation of genes that mostly related to inflammation [9,10], suggesting that NAV-3 has a role in linking inflammation to cancer development.…”

“…Navigator-3 (NAV-3) was first found and mentioned as a novel cancer-associated gene that contributes to the pathogenesis of the basal and squamous cell cancers [9]. Silencing of NAV-3 leads to the variation of genes that mostly related to inflammation [9,10], suggesting that NAV-3 has a role in linking inflammation to cancer development. In addition, Cohen-Dvashi H et al discovered that silencing of NAV-3 increased metastasis in breast cancer animal model, indicating that NAV-3 might play an metastasis-suppressing role in breast cancer [11].…”

Potential role of a navigator gene NAV3 in colorectal cancer

“…Most of these general characteristics of a causative factor apply to NAV3, as demonstrated by others and us. Frequent NAV3 copy number changes were identified in CTCL (Karenko et al , 2005) and in two other epithelial cancers: basocellular and squamocellular carcinomas of the skin (Maliniemi et al , 2011). In CTCL, deletion of NAV3 correlated with poor prognosis or with poor response to therapy (Ranki et al , 2011).…”

“…25% of cutaneous basal and squamous cell cancers (Maliniemi et al , 2011). NAV3 mutations and copy number changes have thereafter been reported in melanoma (Bleeker et al , 2009) and in human glioblastomas, respectively (Nord et al , 2009).…”