Involvement of transcribed lncRNA uc.291 and SWI/SNF complex in cutaneous squamous cell carcinoma

Abstract

While non-melanoma skin cancers (NMSCs) are the most common tumours in humans, only the sub-type cutaneous squamous cell carcinoma (cSCC), might become metastatic with high lethality. We have recently identified a regulatory pathway involving the lncRNA transcript uc.291 in controlling the expression of epidermal differentiation complex genes via the interaction with ACTL6A, a component of the chromatin remodelling complex SWI/SNF. Since transcribed ultra-conserved regions (T-UCRs) are expressed in normal tissues and are deregulated in tumorigenesis, here we hypothesize a potential role for dysregulation of this axis in cSCC, accounting for the de-differentiation process observed in aggressive poorly differentiated cutaneous carcinomas. We therefore analysed their expression patterns in human tumour biopsies at mRNA and protein levels. The results suggest that by altering chromatin accessibility of the epidermal differentiation complex genes, down-regulation of uc.291 and BRG1 expression contribute to the de-differentiation process seen in keratinocyte malignancy. This provides future direction for the identification of clinical biomarkers in cutaneous SCC. Analysis of publicly available data sets indicates that the above may also be a general feature for SCCs of different origins.

Gene expression in organoids: an expanding horizon

“…Epigenetic modifications of chromatin are crucial for regulation of gene expression and are precisely regulated by a complex network of interaction between transcription factors, chromatin remodellers [ 163 ] and even non-coding RNAs [ 57 , 164 , 165 ]. Identification of genomic regulatory elements and study of epigenetic state of chromatin historically has been achieved through analyse of DNA occupancy by distinct transcription factors (TFs) and histone modifications.…”

Ultra-conserved RNA: a novel biological tool with diagnostic and therapeutic potential

“…The gene ACTL6A was found to regulate the SWI/SNF chromatin remodeling complex as a carcinogen in squamous cell carcinoma to maintain the tumor in an undifferentiated state. Interestingly, uc.291 can act negatively on ACTL6A , reversing the inhibition of differentiation genes mediated by ACTL6A [ 58 ].…”

Distinct interactors define the p63 transcriptional signature in epithelial development or cancer

“…Interestingly, both ACTL6A and TP63 are co-amplified in HNSCC, they are also physically co-associated and co-expressed together with other BAF complex subunits co-regulating a key set of relevant targets, including genes encoding components of the Hippo-YAP signaling pathway ( Figure 3a ) [ 64 ]. These findings indicated that p63/BAF function together in a common pathway to counteract differentiation both in normal epithelial progenitor cells and in tumor cells [ 57 , 64 ].…”