Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and frequently progresses from an actinic keratosis (AK), a sun-induced keratinocyte intraepithelial neoplasia (KIN). Epigenetic mechanisms involved in the phenomenon of progression from AK to cSCC remain to be elicited.
Methods: Expression of microRNAs in sun-exposed skin, AK and cSCC was analysed by Agilent microarrays. DNA methylation of miR-204 promoter was determined by bisulphite treatment and pyrosequencing. Identification of miR-204 targets and pathways was accomplished in HaCat cells. Immunofluorescence and immunohistochemistry were used to analyze STAT3 activation and PTPN11 expression in human biopsies.
Results: cSCCs display a marked downregulation of miR-204 expression when compared to AK. DNA methylation of miR-204 promoter was identified as one of the repressive mechanisms that accounts for miR-204 silencing in cSCC. In HaCaT cells miR-204 inhibits STAT3 and favours the MAPK signaling pathway, likely acting through PTPN11, a nuclear tyrosine phosphatase that is a direct miR-204 target. In non-peritumoral AK lesions, activated STAT3, as detected by pY705-STAT3 immunofluorescence, is retained in the membrane and cytoplasm compartments, whereas AK lesions adjacent to cSCCs display activated STAT3 in the nuclei.
Conclusions: Our data suggest that miR-204 may act as a "rheostat" that controls the signalling towards the MAPK pathway or the STAT3 pathway in the progression from AK to cSCC.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960761 | PMC |
| http://dx.doi.org/10.1186/s12943-016-0537-z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Comprehensive analysis of ferroptosis-related genes reveals potential therapeutic targets in osteoporosis patients: a computational analysis and experiments.
Front Genet
January 2025
Department of Orthopedics, First Hospital of Jiaxing, Jiaxing, China.
Background: Ferroptosis-related genes have been reported to play important roles in many diseases, but their molecular mechanisms in osteoporosis have not been elucidated.
Methods: Based on two independent GEO datasets (GSE35956 and GSE35958), and GSE35959 as the validation dataset, we comprehensively elucidated the pathological mechanism of ferroptosis-related genes in osteoporosis by GO analyses, KEGG analyses and a PPI network. Then, We used Western Blot (WB) and Quantitative real-time polymerase chain reaction (qPCR) to verify the expression level of KMT2D, a ferroptosis-related hub gene, in clinical samples.
Transcription factor FOXD1 and miRNA-204-5p play a major role in B4GALNT2 downregulation in colon cancer.
Sci Rep
January 2025
Department of Medical and Surgical Sciences (DIMEC), General Pathology Building, University of Bologna, Bologna, Italy.
The β1,4-N-acetylgalactosaminyltransferase 2 (B4GALNT2) which synthesizes the histo-blood group antigen Sd is highly expressed by normal colon, but it is dramatically down-regulated in colorectal cancer (CRC). High B4GALNT2 expression in CRC tissues is a marker of longer survival. The molecular bases of B4GALNT2 inhibition in CRC are largely obscure.
View Article and Find Full Text PDFHypothyroidism induced by excessive-iodine is associated in humans with altered hsa-miR-199a-5p/HIF-1α axis and thyroglobulin.
J Nutr Biochem
January 2025
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin, 150081, China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin, 150081, China.. Electronic address:
The adverse effect of excessive iodine intake has attracted extensive attention. However, the role of excessive iodine on hypothyroidism and detailed mechanism are not exactly known. Studies have shown that miRNAs are crucial to the occurrence and development of hypothyroidism.
View Article and Find Full Text PDFManaging cardiovascular events, hyperglycemia, and obesity in type 2 diabetes through microRNA regulation linked to glucagon-like peptide-1 receptor agonists.
Diabetol Metab Syndr
January 2025
Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.
Background And Aims: Type 2 diabetes mellitus (T2DM) is usually complicated by cardiovascular diseases, hyperglycemia, and obesity, which worsen the outcome for the patient. Since recent evidence underlines the epigenetic role of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the management of these comorbidities, this study compared the effects of these agents, namely liraglutide, semaglutide, dulaglutide, and exenatide, on miRNA regulation in the management of T2DM.
Results: GLP-1RAs modify the expression of miRNAs involved in endothelial function, sugar metabolism, and adipogenesis, including but not limited to miR-27b, miR-130a, and miR-210.
MicroRNA-204-5p Deficiency within the vmPFC Region Contributes to Neuroinflammation and Behavioral Disorders via the JAK2/STAT3 Signaling Pathway in Rats.
Adv Sci (Weinh)
January 2025
Key Laboratory of Mental Disorders, The Second Hospital of Shandong University, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, 250012, China.
Major depressive disorder (MDD) is usually considered associate with immune inflammation and synaptic injury within specific brain regions. However, the molecular mechanisms underlying the neural deterioration resulting in depression remain unclear. Here, it is found that miR-204-5p is markedly downregulated in the ventromedial prefrontal cortex (vmPFC) in a chronic unpredictable mild stress (CUMS) induce rat model of depression.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!