Deciphering the Molecular Landscape of Cutaneous Squamous Cell Carcinoma for Better Diagnosis and Treatment

Lazăr, Andreea Daniela; Dinescu, Sorina; Costache, Marieta

doi:10.3390/jcm9072228

Cited by 25 publications

(38 citation statements)

References 132 publications

(250 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Based on the results of the molecular mechanism study, knockdown of lncRNA NEAT1 significantly inhibited metalloproteinase-2, and -9, N-cadherin, and vimentin expression and promoted the expression of E-cadherin. CSCC, which originates from keratinocytes, is the second most common form of nonmelanoma skin cancer and one of the primary causes of nonmelanoma skin cancerrelated death (19). Overexpression of some lncRNAs has been found in a number of tumor tissues and thus can be considered potential biomarkers or targets for future diagnosis and treatment of squamous cell carcinoma (17).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of lncRNA NEAT1 inhibits the proliferation of human cutaneous squamous cell carcinoma in vivo and in vitro

Shen¹,

Huang²,

Zhang³

et al. 2022

Ann Transl Med

View full text Add to dashboard Cite

Background: The incidence of cutaneous squamous cell carcinoma (CSCC), a malignant tumor that threatens human life, is increasing every year, and yet its pathogenesis is still unclear. This study found that long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) was abnormally expressed in CSCC. However, the biochemical mechanisms of lncRNA NEAT1 in carcinogenesis and the development of cancer remain unclear.Methods: Fluorescence quantitative polymerase chain reaction (qPCR) was conducted to determine lncRNA NEAT1 expression in CSCC and paracarcinoma tissues and investigate the correlation between NEAT1 levels and patients' clinicopathological features. The invasion, proliferation, and migration of CSCC cells were measured using colony formation, Cell Counting Kit-8, and Transwell assays. Western blot assay was conducted to test whether NEAT1 knockdown affected invasion and migration-related proteins. In addition, a nude mouse subcutaneous tumorigenesis experiment was performed to determine whether the knockdown of NEAT1 affected the proliferation ability of CSCC cells.Results: Changes in lncRNA NEAT1 expression in CSCC tissues were correlated with the degree of lymph node metastasis and the tumor, regional lymph nodes, and distant metastasis (TNM) grade of patients. The downregulation of NEAT1 lncRNA significantly impeded cell invasion, proliferation, and migration in CSCC. Through lncRNA NEAT1 knockdown, significant reductions in metalloproteinase-2, metalloproteinase-9, N-cadherin, and vimentin expression were observed, and the level of E-cadherin increased. In vivo experiments in nude mice revealed that knockdown of lncRNA NEAT1 greatly inhibited cell proliferation in CSCC. Conclusions:In CSCC tissues, NEAT1 lncRNA was expressed at high levels and correlated with lymph node metastasis and TNM stage. The knockdown of NEAT1 lncRNA could significantly impede CSCC proliferation, metastasis, and invasion. Additionally, by measuring the expression level of lncRNA NEAT1, we may be able to detect the clinical and pathological characteristics of CSCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Downregulation of lncRNA NEAT1 inhibits the proliferation of human cutaneous squamous cell carcinoma in vivo and in vitro

Shen¹,

Huang²,

Zhang³

et al. 2022

Ann Transl Med

View full text Add to dashboard Cite

show abstract

“…Co ciekawe, wg bazy Bioportal częstość mutacji w genie RIPK4 (domena kinazowa i powtórzeń ankirynowych) jest najwyższa w SCC (w 20% przypadków) w porównaniu do innych nowotworów, np. dla czerniaka wynosi ok 6%, jajnika 1%, dla pozostałych <1% [43,44]. Zwiększony rozrost guzów SCC u myszy z indukowaną delecją Ripk4, a także niższy poziom ekspresji RIPK4 w SCC u ludzi w porównaniu do skóry zdrowej [26], sugeruje, że białko to w skórze może pełnić funkcję supresora nowotworów [10].…”

Section: Ripk4 a Raki Skóryunclassified

Rola białka RIPK4 w fizjologii naskórka.

2021

View full text Add to dashboard Cite

Białka regulujące morfogenezę naskórka zapewniają jego prawidłowa budowę oraz funkcję. Mutacje w ich obrębie prowadzą do licznych zaburzeń w pełnionej funkcji. Jednym z takich ostatnio opisanych białek jest kinaza białkowa oddziałująca z receptorem kinaz serynowo-treoninowych 4 (RIPK4). Kinaza ta w naskórku pełni ważną funkcję regulatora homeostazy pomiędzy proliferacja a różnicowaniem się keratynocytów. Mutacje w obrębie genu kodującego białko RIPK4 skutkują u ludzi letalnym zespołem Bartsocas-Papas lub zespołem mnogich płetwistości typu Aslana, a jego delecja u myszy (Ripk4-/-) prowadzi do przedwczesnej śmierci noworodków spowodowanej licznymi zrostami skórnymi. RIPK4 odgrywa rolę w stanie zapalnym skóry. Sugeruje się, że białko to w skórze pełni rolę supresora nowotworów, ponieważ jego poziom zmniejsza się w rakach kolczystokomórkowych względem skóry zdrowej, a jego indukowana delecja w modelu mysim sprzyja powstawaniu i rozrostowi brodawczaków i raków kolczystokomórkowych wywoływanych na drodze chemicznej. W pracy omówiono rodzinę białek RIP, udział białka RIPK4 w różnicowaniu się naskórka i szlakach sygnalizacyjnych, a także konsekwencje zaburzeń wywołanych jego nieprawidłową ekspresją.

show abstract

“…Gene expression profiles of tumor tissues have revolutionized our understandings on cSCC [ 10 ]. Yet most analyses of gene expression are dominated by bulk RNA-sequencing (RNA-seq) technology, in which the expression profile of each gene is profiled by the average expression of all sequenced cells for each biological sample, masking many critical aspects of intra-tumor heterogeneity (ITH) and hindering our understandings of cSCC biology.…”

Section: Introductionmentioning

confidence: 99%

Single-cell transcriptomic analysis reveals the critical molecular pattern of UV-induced cutaneous squamous cell carcinoma

et al. 2021

View full text Add to dashboard Cite

Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer characterized by high invasiveness, heterogeneity, and mainly occurs in the ultraviolet (UV)-exposed regions of the skin, but its pathogenesis is still unclear. Here, we generated single-cell transcriptome profiles for 350 cells from six primary UV-induced cSCCs, together with matched adjacent skin samples, and three healthy control skin tissues by single-cell RNA-sequencing technology based on Smart-seq2 strategy. A series of bioinformatics analyses and in vitro experiments were used to decipher and validate the critical molecular pattern of cSCC. Results showed that cSCC cells and normal keratinocytes were significantly distinct in gene expression and chromosomal copy number variation. Furthermore, cSCC cells exhibited 18 hallmark pathways of cancer by gene set enrichment analysis. Differential expression analysis demonstrated that many members belonging to S100 gene family, SPRR gene family, and FABP5 were significantly upregulated in cSCC cells. Further experiments confirmed their upregulation and showed that S100A9 or FABP5 knockdown in cSCC cells inhibited their proliferation and migration through NF-κB pathway. Taken together, our data provide a valuable resource for deciphering the molecular pattern in UV-induced cSCC at a single-cell level and suggest that S100A9 and FABP5 may provide novel targets for therapeutic intervention of cSCC in the future.

show abstract

Deciphering the Molecular Landscape of Cutaneous Squamous Cell Carcinoma for Better Diagnosis and Treatment

Cited by 25 publications

References 132 publications

Downregulation of lncRNA NEAT1 inhibits the proliferation of human cutaneous squamous cell carcinoma in vivo and in vitro

Downregulation of lncRNA NEAT1 inhibits the proliferation of human cutaneous squamous cell carcinoma in vivo and in vitro

Rola białka RIPK4 w fizjologii naskórka.

Single-cell transcriptomic analysis reveals the critical molecular pattern of UV-induced cutaneous squamous cell carcinoma

Contact Info

Product

Resources

About