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Cutaneous squamous cell carcinoma (cSCC) ranks as the second most prevalent skin tumour (excluding melanoma). However, the molecular mechanisms driving cSCC progression remain elusive. This study aimed to investigate GBP1 expression in cSCC and elucidate its potential molecular mechanisms underlying cSCC development. GBP1 expression was assessed across public databases, cell lines and tissue samples. Various assays, including clone formation, CCK8 and EdU were employed to evaluate cell proliferation, while wound healing and transwell assays determined cell migration and invasion. Subcutaneous tumour assays were conducted to assess in vivo tumour proliferation, and molecular mechanisms were explored through western blotting, immunofluorescence and immunoprecipitation. Results identified GBP1 as an oncogene in cSCC, with elevated expression in both tumour tissues and cells, strongly correlating with tumour stage and grade. In vitro and in vivo investigations revealed that increased GBP1 expression significantly enhanced cSCC cell proliferation, migration and invasion. Mechanistically, GBP1 interaction with SP1 promoted STAT3 activation, contributing to malignant behaviours. In conclusion, the study highlights the crucial role of the GBP1/SP1/STAT3 signalling axis in regulating tumour progression in cSCC. These findings provide valuable insights into the molecular mechanisms of cSCC development and offer potential therapeutic targets for interventions against cSCC. [ABSTRACT FROM AUTHOR]

Background: THOC7-AS1 and FSTL1 expression are frequently upregulated in cutaneous squamous cell carcinoma (cSCC). However, their molecular biological mechanisms remain elusive and their potential as therapeutic targets needs urgent exploration. Methods: Human tissue samples were used to evaluate clinical parameters. In vitro and in vivo experiments assessed biological functions. Quantitative PCR, western blot, immunohistochemistry, immunocytochemistry, immunoprecipitation, RNA fluorescence in situ hybridization, RNA pull-down, RNA immunoprecipitation, silver staining, chromatin immunoprecipitation, dual luciferase reporter assays etc. were utilized to explore the molecular biological mechanisms. Results: We found FSTL1 is an oncogene in cSCC, with high expression in tumor tissues and cells. Its elevated expression closely associates with tumor size and local tissue infiltration. In vitro and in vivo, high FSTL1 expression promotes cSCC proliferation, migration and invasion, facilitating malignant behaviors. Mechanistically, FSTL1 interacts with ZEB1 to promote epithelial-to-mesenchymal transition (EMT) in cSCC cells. Exploring upstream regulation, we found THOC7-AS1 can interact with OCT1, which binds the FSTL1 promoter region and promotes FSTL1 expression, facilitating cSCC progression. Finally, treating tumors with THOC7-AS1 antisense oligonucleotides inhibited cSCC proliferative and migratory abilities, delaying tumor progression. Conclusions: The THOC7-AS1/OCT1/FSTL1 axis regulates EMT and promotes tumor progression in cSCC. This study provides clues and ideas for cSCC targeted therapy. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) modulates RNA metabolism and functions in cell differentiation, tissue development, and immune response. After acute burns, skin wounds are highly susceptible to infection and poor healing. However, our understanding of the effect of burn injuries on m6A methylation and their potential mechanism is still limited. Human m6A-mRNA&lncRNA Epitranscriptomic microarray was used to obtain comprehensive mRNA and lncRNA transcriptome m6A profiling and gene expression patterns after burn injuries in human skin tissue. Bioinformatic and functional analyses were conducted to find molecular functions. Microarray profiling showed that 65 mRNAs and 39 lncRNAs were significantly hypermethylated; 5492 mRNAs and 754 lncRNAs were significantly hypomethylated. Notably, 3989 hypomethylated mRNAs were down-expressed and inhibited many wound healing biological processes and pathways including in the protein catabolic process and supramolecular fiber organization pathway; 39 hypermethylated mRNAs were up-expressed and influenced the cell surface receptor signaling pathway and inflammatory response. Moreover, we validated that m6A regulators (METTL14, METTL16, ALKBH5, FMR1, and HNRNPC) were significantly downregulated after burn injury which may be responsible for the alteration of m6A modification and gene expression. In summary, we found that homeostasis in the skin was disrupted and m6A modification may be a potential mechanism affecting trauma infection and wound healing. [ABSTRACT FROM AUTHOR]

Thermal injury repair is a complex process during which the maintenance of the proliferation and migration of human skin fibroblasts (HSFs) exert a crucial role. MicroRNAs have been proven to exert an essential function in repairing skin burns. This study delves into the regulatory effects of miR‐24‐3p on the migration and proliferation of HSFs that have sustained a thermal injury, thereby, providing deeper insight into thermal injury repair pathogenesis. The PPAR‐β protein expression level progressively increased in a time‐dependent manner on the 12th, 24th and 48th hour following the thermal injury of the HSFs. The knockdown of PPAR‐β markedly suppressed the proliferation of and migration of HSF. Following thermal injury, the knockdown also promoted the inflammatory cytokine IL‐6, TNF‐α, PTGS‐2 and P65 expression. PPAR‐β contrastingly exhibited an opposite trend. A targeted relationship between PPAR‐β and miR‐24‐3p was predicted and verified. miR‐24‐3p inhibited thermal injured HSF proliferation and migration and facilitated inflammatory cytokine expression through the regulation of PPAR‐β. p65 directly targeted the transcriptional precursor of miR‐24 and promoted miR‐24 expression. A negative correlation between miR‐24‐3p expression level and PPAR‐β expression level in rats' burnt dermal tissues was observed. Our findings reveal that miR‐24‐3p is conducive to rehabilitating the denatured dermis, which may be beneficial in providing effective therapy of skin burns. [ABSTRACT FROM AUTHOR]

Our previous study confirmed the critical role of miR‐125b and vascular endothelial growth factor (VEGF) in burn wound repair., The present study was aimed to identify the role of long noncoding RNAs (lncRNAs) related to the function of miR‐125b and VEGF in burn wound repair and the underlying mechanism. First, we found that lncRNA PDK1‐AS and VEGFA expression was significantly increased in heat‐denatured dermal tissue samples and in human dermal microvascular endothelial cells (HDMECs) and human umbilical vein endothelial cells (HUVECs) after thermal injury. PDK1‐AS knockdown significantly inhibited cell viability, cumulative tube length, cell migratory ability, and cell invasion of thermally injured HDMECs and HUVECs. PDK1‐AS knockdown decreased VEGFA protein levels in HDMECs and HUVECs. While overexpression of PDK1‐AS showed the opposite effects. Online tools prediction and luciferase assay confirmed that miR‐125b‐5p targeted PDK1‐AS and VEGFA 3′‐untranslated region. miR‐125b‐5p inhibition significantly increased VEGFA protein levels and enhanced viability, cumulative tube length, migratory ability, and invasion of HUVECs and HDMECs. Furthermore, the effects of PDK1‐AS knockdown on VEGFA protein levels in the two cell lines were partially reversed by miR‐125b‐5p inhibition. Finally, in the tissue samples, PDK1‐AS and VEGFA expression was increased, while miR‐125b‐5p expression was decreased in heat‐denatured dermal tissues; the expression of miR‐125b‐5p had a negative correlation with PDK1‐AS and VEGFA, respectively, and PDK1‐AS and VEGFA were positively correlated with each other in tissue samples. In conclusion, PDK1‐AS relieves miR‐125b‐5p‐induced inhibition on VEGFA by acting as a endogenous RNA, therefore modulating HDMEC and HUVEC angiogenesis after thermal injury. [ABSTRACT FROM AUTHOR]

Fibrosarcoma is a highly malignant type of soft tissue sarcoma that currently lacks effective treatment options. Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12) belongs to the uridine diphosphate N-acetylgalactosamine gene family, which is involved in numerous biological processes of diseases, such as tumor progression. Its upregulated expression is closely associated with the development of colorectal cancer. However, research on the role of GALNT12 in fibrosarcoma is currently limited. The present study aimed to assess the expression and biological function of GALNT12 in fibrosarcoma. Patient data and tissue samples were collected and public datasets were obtained from the Gene Expression Omnibus (GSE24369 and GSE21124). Immunofluorescence assays were performed to observe the cellular localization of GALNT12. GALNT12 expression was measured using reverse transcription-quantitative PCR, western blotting and immunohistochemistry. Small interfering RNAs were constructed to knock down GALNT12 expression in HT-1080 cells. Cell Counting Kit-8 and EdU assays were used to assess fibrosarcoma cell proliferation. Wound healing and Transwell assays were used to detect migration. Gene set enrichment analysis was performed to identify key pathways. Paired and unpaired Student's t-test, Fisher's exact test and one-way ANOVA (followed by Tukey's Honest Significant Difference test) were used to analyze the data. It was demonstrated that GALNT12 expression was upregulated in both fibrosarcoma cell lines and tissue samples and predicted poor patient prognosis. In vitro experiments demonstrated that high GALNT12 expression levels significantly increased HT-1080 cell proliferation and migration. Furthermore, it was demonstrated that high GALNT12 expression levels were closely associated with the yes1 associated transcriptional regulator (YAP1) signaling pathway. Knockdown of GALNT12 inhibited YAP1 nuclear translocation, which affected activation of key downstream genes including AMOTL2, BIRC5 and CYR61. Therefore, the present study demonstrated that GALNT12 promoted fibrosarcoma progression. GALNT12 could be a potential biomarker for this disease and may potentially provide new ideas for targeted therapy of fibrosarcoma in the future. [ABSTRACT FROM AUTHOR]