Project description:Analysis of sncRNA expression in 22 primary cSCC (10 from cSCCs that had evolved to histologically confirmed metastases, or MSCC, and 12 from a cSCC control group who had not developed any metastasis in a 5-year follow-up period). Unsupervised hierarchical clustering of the most variably expressed sncRNAs stratified the tumors into two groups, one formed mainly by NMSCC and the other formed exclusively by metastasizing cSCC, the latter displaying an overall sncRNA downregulation. Supervised clustering of MSCC vs. NMSCC identified the differential expression of 330 sncRNAs, most of them downregulated in the metastasizing group (248 sncRNAs; 75%). Functional and sequence-based classification of the probes in the array revealed alterations in the proportion of the snoRNAs represented in MSCCs when compared to their expression in NMSCCs.
Project description:Cutaneous squamous cell carcinoma (cSCC) is the leading cause of death in recessive dystrophic epidermolysis bullosa (RDEB) patients but remains poorly studied on a proteomic level. We aim to characterize the RDEB-SCC proteome by comparing it to the proteomes of UV-light induced cSCC of non-aggressive and aggressive behavior with which RDEB cSCC share either the well-differentiated morphology or the aggressive behavior, respectively. We applied a direct trypsinization protocol using an acid labile surfactant and label-free quantitation to study formalin-fixed, paraffin-embedded tissues from patients with RDEB cSCC (n=6), low-risk cSCC (n=5) and metastasizing cSCC (n=13) by liquid chromatography tandem-mass spectrometry.
Project description:Keratinocyte carcinomas (BCC and cSCC) are the most common cancers worldwide. cSCC is considered as the most prevalent metastatic skin malignancy and its incidence is increasing globally. The complement system is a fundamental part of the host immune defense. It is composed of three distinct pathways (classical, alternative and lectin) that get activated sequentially. However, the process of complement activation is rigorously regulated by a series of soluble and membrane-bound inhibitor proteins that protect the host cells from lytic damage. One of these soluble negative regulators is complement factor I (CFI) which is an 88 kDa serine protease that hampers all three complement pathways through blockade of C3- and C5- convertases by cleaving C3b and C4b. Oligonucleotide array (Affymetrix)-based analysis of normal human epidermal keratinocytes (NHEKs; n=5), primary (Prim. cSCC; n=5) and metastatic (Met. cSCC; n=3) cSCC cell lines as well as next-generation-sequencing (SOLiD) based transcriptome profiling of NHEKs (n=4), primary (Prim. cSCC; n=5) and metastatic (Met. cSCC; n=3) cSCC cell lines revealed marked overexpression of CFI in cSCC cells compared to NHEKs (GSE66368 and GSE66412 respectively). Furthermore, we have previously shown that knockdown of CFI inhibits proliferation and migration of cSCC cells and potently impedes growth of cSCC xenograft tumors in vivo. In these respects, we intended to further investigate the functional role and molecular mechanism of CFI in cSCC progression via analyzing the mRNA expression profile of CFI in cSCC cells.
Project description:Punch biopsies from patients with cSCC (n=3) and non-lesional skin (n=3) were included in the study. Microarray based circRNA expression profiles were acquired using Arraystar circRNA Arrays V. 2.0 screening for 13.617 distinct human circRNA candidates. We identified circRNAs differentially expressed in cSCC compared to non-lesional skin (control).
Project description:In the present study, we aim to identify key genes or pathways in the progression from normal skin to actinic keratoses (AK), then to cutaneous squamous cell carcinoma (cSCC) by transcriptomics analysis. We firstly established a UVR-induced cSCC model using SKH-1 hairless mouse successfully. Then, the transcriptome profiles among normal skin, AK and cSCC were investigated. We also constructed pseudo trajectory and deconvoluted the cell compositions among these three different tissues. A series of bioinformatics and molecular experiments analyses were carried out and we found retinoic acid receptor-related receptor alpha (Rora) was involved in this progression. Our results demonstrated Rora can be a potential therapeutic target for cSCC, which facilitates the treatment of cSCC.
Project description:Keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, and its incidence is increasing globally. Chronic inflammation has been recognized as a risk factor for cSCC and inflammation is a typical feature of the progression of actinic keratosis lesions to invasive and metastatic cSCC. Inflammasomes are important components of the innate immune response involved in onset of inflammation. Inflammasome component AIM2 serves as a sensor for cytoplasmic double-strand DNA, and this way plays a key role in response to bacterial and viral colonization. Activation of inflammasome by cytoplasmic DNA in epidermal keratinocytes can promote the initiation of inflammation in autoimmune and autoinflammatory skin diseases. Whole transcriptome analysis of cSCC cells (n=8) and normal human epidermal keratinocytes (NHEKs, n=4) and oligonucleotide array-based expression analysis of cSCC cells (n=8) and normal human epidermal keratinocytes (NHEKs, n=5) revealed overexpression of AIM2 in cSCC cells (GSE66412 and GSE66368, respectively). We wanted to futher study the RNA expression profile of AIM2 knockdown cSCC cells.
Project description:Keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, and its incidence is increasing globally. Long non-coding RNAs (lncRNAs) are involved in various biological processes, and their role in cancer progression is emerging. Whole transcriptome analysis of cSCC cell lines (n=8) and normal human epidermal keratinocytes (NHEKs, n=4) revealed overexpression of long intergenic ncRNA (LINC00346) in cSCC cells (GSE66412). We wanted to futher study the RNA expression profile of LINC00346 knockdown cSCC cells. Based on our observations, LINC00346 was named PRECSIT (p53 regulated carcinoma-associated STAT3-activating long intergenic non-protein coding transcript).
Project description:Keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, and its incidence is increasing globally. Chronic inflammation has been recognized as a risk factor for cSCC and inflammation is a typical feature in the progression of premalignant actinic keratosis lesions to invasive and metastatic cSCC. The complement system is an important part of innate immunity, and activation of complement is detected in the microenvironment of tumors and has been considered a host defense mechanism against cancer cells. The complement cascade can be activated via three distinct pathways, namely the classic, lectin, or alternative pathways, which all lead to activation of lytic pathway and formation of the membrane attack complex, a pore-like structure on the target cell membrane resulting in the lysis of the target cell. The classical pathway of complement is typically activated by binding of C1 complex to antibodies bound to their target antigens. The C1 complex consists of six subcomponents of C1q, each with a collagenous triple helix of subunits C1qA, C1qB, and C1qC chains and two copies of serine proteases C1r and C1s subunits each. Whole transcriptome analysis of cSCC cells (n=8) and normal human epidermal keratinocytes (NHEKs, n=4) and oligonucleotide array-based expression analysis of cSCC cells (n=8) and normal human epidermal keratinocytes (NHEKs, n=5) revealed overexpression of C1r in cSCC cells (GSE66412 and GSE66368, respectively). Previously it has been shown that knockdown of C1r promotes apoptosis of cSCC cells and significantly suppresses growth and vascularization of human cSCC xenograft tumors in vivo (Riihilä et al. Br J Dermatol 2020; 182:658-670). In this respect, we have studied the RNA expression profile of cSCC cells after C1r knockdown.