Long non-coding RNAs in cutaneous biology and keratinocyte carcinomas

Long non-coding RNAs (lncRNAs) are a largely uncharacterized group of non-coding RNAs with diverse regulatory roles in various biological processes. Recent observations have elucidated the functional roles of lncRNAs in cutaneous biology, e.g. in proliferation and differentiation of epidermal keratinocytes and in cutaneous wound repair. Furthermore, the role of lncRNAs in keratinocyte-derived skin cancers is emerging, especially in cutaneous squamous cell carcinoma (cSCC), which presents a significant burden to health care services worldwide and causes high mortality as metastatic disease. Elucidation of the functions of keratinocyte-specific lncRNAs will improve understanding of the molecular pathogenesis of epidermal disorders and skin cancers and can be exploited in development of new diagnostic and therapeutic applications for keratinocyte carcinomas. In this review, we summarize the current evidence of functionally important lncRNAs in cutaneous biology and in keratinocyte carcinomas.</p

Matrix metalloproteinases in keratinocyte carcinomas

The incidence of cutaneous keratinocyte-derived cancers is increasing globally. Basal cell carcinoma (BCC) is the most common malignancy worldwide, and cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer. BCC can be classified into subtypes based on the histology, and these subtypes are classified further into low- and high-risk tumors. There is an increasing need to identify new therapeutic strategies for the treatment of unresectable and metastatic cSCC, and for aggressive BCC variants such as infiltrating, basosquamous or morpheaform BCCs. The most important risk factor for BCC and cSCC is solar UV radiation, which causes genetic and epigenetic alterations in keratinocytes. Similar gene mutations are noted already in sun-exposed normal skin emphasizing the role of the alterations in the tumor microenvironment in the progression of cSCC. Early events in cSCC progression are alterations in the composition of basement membrane and dermal extracellular matrix induced by influx of microbes, inflammatory cells and activated stromal fibroblasts. Activated fibroblasts promote inflammation and produce growth factors and proteolytic enzymes, including matrix metalloproteinases (MMPs). Transforming growth factor-beta produced by tumor cells and fibroblasts induces the expression of MMPs by cSCC cells and promotes their invasion. Fibroblast-derived keratinocyte growth factor suppresses the malignant phenotype of cSCC cells by inhibiting the expression of several MMPs. These findings emphasize the importance of interplay of tumor and stromal cells in the progression of cSCC and BCC and suggest tumor microenvironment as a therapeutic target in cSCC and aggressive subtypes of BCC

Nurmipalkokasvit vertailussa - puna-apila satoisin, vuohenherne pitkäikäisin

Puna-apila on satoisin nurmipalkokasvi lyhytikäisissä nurmissa. Vuohenherne säilyy nurmessa parhaiten ja kasvattaa satoaan nurmen vanhetessa. Valkoapila puolestaan paikkaa parhaiten talvituhojen tekemät aukot. Sinimailasen viljelytekniikka tarvitsee vielä paljon tarkennusta.vo

Pitkät ei-koodaavat RNA:t ihosyövässä

Pitkät ei-koodaavat RNA:t (long non-coding RNA, lncRNA) ovat laaja ja toiminnoiltaan monipuolinen joukko geenien säätelijämolekyylejä, joilla on tärkeä rooli solujen normaalin toiminnan ja tasapainon ylläpidossa. Ihossa ne osallistuvat muun muassa keratinosyyttien erilaistumisen ja haavan paranemisen säätelyyn. LncRNA:iden poikkeava ilmentyminen on havaittu lukuisissa eri syövissä, mukaan lukien ihosyövissä, kuten melanoomassa ja okasolusyövässä. Lisääntyvä tutkimusnäyttö lncRNA:iden toimintamekanismeista ihosyöpien kehittymisessä avaa uusia näkökulmia niiden käyttömahdollisuuksista ihosyöpien diagnostiikassa, luokittelussa ja uusien hoitomuotojen kehittämisessä

Complement factor I upregulates expression of matrix metalloproteinase-13 and-2 and promotes invasion of cutaneous squamous carcinoma cells

The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing globally. Here, we have studied the functional role of complement factor I (CFI) in the progression of cSCC. CFI was knocked down in cSCC cells, and RNA-seq analysis was performed. Significant downregulation of genes in IPA biofunction categories Proliferation of cells and Growth of malignant tumor, in Gene Ontology (GO) terms Metallopeptidase activity and Extracellular matrix component, as well as Reactome Degradation of extracellular matrix was detected after CFI knockdown. Further analysis of the latter three networks, revealed downregulation of several genes coding for invasion-associated matrix metalloproteinases (MMPs) after CFI knockdown. The downregulation of MMP-13 and MMP-2 was confirmed at mRNA, protein and tissue levels by qRT-qPCR, Western blot and immunohistochemistry, respectively. Knockdown of CFI decreased the invasion of cSCC cells through type I collagen. Overexpression of CFI in cSCC cells resulted in enhanced production of MMP-13 and MMP-2 and increased invasion through type I collagen and Matrigel, and in increased ERK1/2 activation and cell proliferation. Altogether, these findings identify a novel mechanism of action of CFI in upregulation of MMP-13 and MMP-2 expression and cSCC invasion. These results identify CFI as a prospective molecular marker for invasion and metastasis of cSCC.Peer reviewe

Long non-coding RNA PICSAR decreases adhesion and promotes migration of squamous carcinoma cells by downregulating α2β1 and α5β1 integrin expression

Long non-coding RNAs (lncRNAs) regulate various cellular processes, and they have emerged as potential biomarkers and therapeutic targets in cancer. We have previously characterized the oncogenic role of lncRNA PICSAR (p38 inhibited cutaneous squamous cell carcinoma associated lincRNA) in cutaneous squamous cell carcinoma (cSCC), the most common metastatic skin cancer. In this study, we show that knockdown of PICSAR in cSCC cells upregulates expression of α2, α5 and β1 integrins, resulting in increased cell adhesion and decreased cell migration on collagen I and fibronectin. In contrast, overexpression of PICSAR in cSCC cells downregulates expression of α2, α5 and β1 integrins on cell surface, resulting in decreased cell adhesion on collagen I and fibronectin and increased cell migration. These results demonstrate a novel mechanism for regulation of the expression of collagen and fibronectin binding integrins by lncRNA PICSAR, leading to altered adhesion and migration of cSCC cells.</p

The role of p53 in progression of cutaneous squamous cell carcinoma

Skin cancers are the most common types of cancer worldwide, and their incidence is increasing. Melanoma, basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC) are the three major types of skin cancer. Melanoma originates from melanocytes, whereas BCC and cSCC originate from epidermal keratinocytes and are therefore called keratinocyte carcinomas. Chronic exposure to ultraviolet radiation (UVR) is a common risk factor for skin cancers, but they differ with respect to oncogenic mutational profiles and alterations in cellular signaling pathways. cSCC is the most common metastatic skin cancer, and it is associated with poor prognosis in the advanced stage. An important early event in cSCC development is mutation of the TP53 gene and inactivation of the tumor suppressor function of the tumor protein 53 gene (TP53) in epidermal keratinocytes, which then leads to accumulation of additional oncogenic mutations. Additional genomic and proteomic alterations are required for the progression of premalignant lesion, actinic keratosis, to invasive and metastatic cSCC. Recently, the role of p53 in the invasion of cSCC has also been elucidated. In this review, the role of p53 in the progression of cSCC and as potential new therapeutic target for cSCC will be discussed. </p

Fruit, Vegetable, and Fibre Intake among Finnish Preschoolers in Relation to Preschool-Level Facilitators and Barriers to Healthy Nutrition

Preschool is a major factor affecting food consumption among young children in Finland, given that most preschoolers eat three meals a day in that setting. Thus, it is important to recognise the determinants of dietary intake at preschool. The aim of this study was to examine food-related factors at the preschool and manager level, and their association with the dietary intake of children in childcare. The study was a part of the cross-sectional DAGIS survey conducted in 2015 to 2016 in Finland. The managers of 58 preschools filled in a questionnaire related to food and nutrition at their preschools. Preschool personnel kept food records for the children (n = 585) on two preschool days. Multilevel linear and logistic regression analyses were conducted with age, gender, and municipality as covariates, preschool-level factors as independent variables, and children’s vegetable (g/day) and fruit (yes vs. no) consumption and fibre intake (g/MJ) as outcome variables. Having many written food policies in the preschool was associated with a higher intake of vegetables (p = 0.01) and fibre (p = 0.03) among the children. Having at least two out of three cooperation-related challenges with the catering service was associated with a higher intake of fibre (p = 0.03) and lower odds of eating fruit (p = 0.01). Factors that are relatively distal from meal situations may have an effect, and should be taken into account in the promotion of healthy eating at preschool, but more studies are needed