Detection and Analysis of the Hedgehog Signaling Pathway-Related Long Non-Coding RNA (lncRNA) Expression Profiles in Keloid

Huang, Heping; Fu, Shangfeng; Liu, Dewu

doi:10.12659/msm.911159

Cited by 26 publications

(20 citation statements)

References 26 publications

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“…A study by Dohi T et al identi ed that the soft skin surrounding keloids is exposed to high mechanical strain that correlates with increased expression of the caveolin-1/rho signaling via the rho kinase mechanotransduction pathway, which may lead to keloid progression. A study by Huang H et al identi ed that upregulated mRNAs were involved in cell proliferation, cell growth, and tissue repair, and downregulated mRNAs were involved in apoptosis [30]. In our study, GO analysis revealed that there were many variations of BP between I group and N group, including regulation of lymphocyte activation and T-cell activation.…”

Section: Discussionsupporting

confidence: 54%

Characteristics of Tumor Immune Gene and Immune Cell Infiltration during Keloid Formation

Líu

Shan

Wang

et al. 2020

Preprint

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Background: Keloids are benign fibroproliferative skin tumors that can cause disfigurement and disability. Although current research has sought to examine keloids from the perspectives of genetics, inflammation, immunity, and tumorigenesis, their pathological mechanisms remain unclear. Methods: In this study, we used three datasets of tumor immune gene expression profiling from the normal skin tissue of keloid patients (N group), inflammation tissue of keloid patients (I group), and keloid tissue of keloid patients (K group) to describe the occurrence and characteristics of keloid development. Tumor immune-related genes were analyzed, and the differentially expressed genes (DEGs) between the three groups were compared. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out to determine the main functions of the differentially expressed genes and keloid-related pathways. Results: We identified several genes that may play an important role in keloid development. These genes are CCR1, SELL, CCR7, CD40LG, CD69, CXCL8, ITGAM, ITGAX, CD86, and CXCL9. GO analysis revealed that there were variations in biological processes (BP) between I group and N group, including regulation of lymphocyte activation and T-cell activation. Similar variations were also found between I group and K group, which may play an important role in keloid initiation and formation. Variations in molecular function (MF) were markedly enriched in cytokine receptor binding and receptor ligand activity. Analysis of the KEGG pathway between I group and N group revealed that DEGs were primarily enriched in cytokine−cytokine receptor interaction and viral protein interaction with cytokine and cytokine receptor. We identified a higher proportion of M2 macrophages in N group than in I group, although the difference was not obvious. M1 macrophage production differed significantly between I group and K group. The proportions of CD8+T cells varied significantly between N group and K group. We traced multiple tumor immune-related hub genes from keloid formation and analyzed immune cell subsets in keloid development. Possible molecular mechanisms were described in this study using bioinformatics. Conclusions: These results provide another possibility to elucidate keloid pathogenesis and therapeutic targets in terms of tumor immune gene expression.

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Section: Discussionsupporting

confidence: 54%

Characteristics of Tumor Immune Gene and Immune Cell Infiltration during Keloid Formation

Líu

Shan

Wang

et al. 2020

Preprint

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“…In keloid tissue, Huang et al found differential expression of 33 mRNAs and 30 lncRNAs relating to the Hh pathway, which were verified by gene chip qPCR. Importantly, by binding the upstream target gene of GLI2 and neighboring target gene HNF1A separately, the lncRNA-AC073257.2 and lncRNA-HNF1A-AS1 could both affect cell keloid growth and proliferation [ 42 ]. It was also confirmed that Wnt-genes were able to orchestrate proliferation and regeneration in skin wound response and keloid.…”

Section: Epigenetic Modification Expression Profile In Keloidmentioning

confidence: 99%

Epigenetic modification mechanisms involved in keloid: current status and prospect

Ren

Hou

et al. 2020

Clin Epigenet

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Keloid, a common dermal fibroproliferative disorder, is benign skin tumors characterized by the aggressive fibroblasts proliferation and excessive accumulation of extracellular matrix. However, common therapeutic approaches of keloid have limited effectiveness, emphasizing the momentousness of developing innovative mechanisms and therapeutic strategies. Epigenetics, representing the potential link of complex interactions between genetics and external risk factors, is currently under intense scrutiny. Accumulating evidence has demonstrated that multiple diverse and reversible epigenetic modifications, represented by DNA methylation, histone modification, and non-coding RNAs (ncRNAs), play a critical role in gene regulation and downstream fibroblastic function in keloid. Importantly, abnormal epigenetic modification manipulates multiple behaviors of keloid-derived fibroblasts, which served as the main cellular components in keloid skin tissue, including proliferation, migration, apoptosis, and differentiation. Here, we have reviewed and summarized the present available clinical and experimental studies to deeply investigate the expression profiles and clarify the mechanisms of epigenetic modification in the progression of keloid, mainly including DNA methylation, histone modification, and ncRNAs (miRNA, lncRNA, and circRNA). Besides, we also provide the challenges and future perspectives associated with epigenetics modification in keloid. Deciphering the complicated epigenetic modification in keloid is hopeful to bring novel insights into the pathogenesis etiology and diagnostic/therapeutic targets in keloid, laying a foundation for optimal keloid ending.

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“…Finally, we analyzed the role and potential mechanism of 5 risk eRNAs. There have been limited PubMed reports on these five eRNAs in cancers, in which the FAM120AOS is highly expressed in colorectal cancer (Akbari et al, 2020) and glioma (Nikas, 2016); the AC073257.2 targeting GLI2, affects the growth and proliferation of cellular keloids (Huang et al, 2018); and the LINC00513 is identified in systemic lupus erythematosus (SLE) and associated with the type I interferon pathway by promoting phosphorylation of STAT1 and STAT2 proteins (Xue et al, 2018). In our study, all risk eRNAs were significantly upregulated in HCC tissues compared to adjacent normal tissues.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of an Immune-Related eRNA Prognostic Signature for Hepatocellular Carcinoma

Cai

Chen

et al. 2021

Front. Genet.

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BackgroundEnhancer RNAs (eRNAs) are intergenic long non-coding RNAs (lncRNAs) that participate in the progression of malignancies by targeting tumor-related genes and immune checkpoints. However, the potential role of eRNAs in hepatocellular carcinoma (HCC) is unclear. In this study, we aimed to construct an immune-related eRNA prognostic model that could be used to prospectively assess the prognosis of patients with HCC.MethodsGene expression profiles of patients with HCC were downloaded from The Cancer Genome Atlas (TCGA). The eRNAs co-expressed from immune genes were identified as immune-related eRNAs. Cox regression analyses were applied in a training cohort to construct an immune-related eRNA signature (IReRS), that was subsequently used to analyze a testing cohort and combination of the two cohorts. Kaplan-Meier and receiver operating characteristic (ROC) curves were used to validate the predictive effect in the three cohorts. Gene Set Enrishment Analysis (GSEA) computation was used to identify an IReRS-related signaling pathway. A web-based cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) computation was used to evaluate the relationship between the IReRS and infiltrating immune cells.ResultsA total of sixty-four immune-related eRNAs (IReRNAs) was identified in HCC, and 14 IReRNAs were associated with overall survival (OS). Five IReRNAs were used for constructing an immune-related eRNA signature (IReRS), which was shown to correlate with poor survival and to be an independent prognostic biomarker for HCC. The GSEA results showed that the IReRS was correlated to cancer-related and immune-related pathways. Moreover, we found that IReRS was correlated to infiltrating immune cells, including CD8+ T cells and M0 macrophages. Finally, differential expressions of the five risk IReRNAs in tumor tissues vs. adjacent normal tissues and their prognostic values were verified, in which the AL445524.1 may function as an oncogene that affects prognosis partly by regulating CD4-CLTA4 related genes.ConclusionOur results suggest that the IReRS could serve as a biomarker for predicting prognosis in patients with HCC. Additionally, it may be correlated to the tumor immune microenvironment and could also be used as a biomarker in immunotherapy for HCC.

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Detection and Analysis of the Hedgehog Signaling Pathway-Related Long Non-Coding RNA (lncRNA) Expression Profiles in Keloid

Cited by 26 publications

References 26 publications

Characteristics of Tumor Immune Gene and Immune Cell Infiltration during Keloid Formation

Characteristics of Tumor Immune Gene and Immune Cell Infiltration during Keloid Formation

Epigenetic modification mechanisms involved in keloid: current status and prospect

Identification and Validation of an Immune-Related eRNA Prognostic Signature for Hepatocellular Carcinoma

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