Time Series Integrative Analysis of RNA Sequencing and MicroRNA Expression Data Reveals Key Biologic Wound Healing Pathways in Keloid-Prone Individuals

Onoufriadis, Alexandros; Hsu, Chao‐Kai; Ainali, Chrysanthi; Ung, Chuin Ying; Rashidghamat, Ellie; Yang, Hsing-San; Huang, Hsin‐Yu; Niazi, Umar; Tziotzios, Christos; Yang, Jui-Chu; Nuamah, Rosamond; Tang, Ming Jer; Saxena, Alka; Rinaldis, Emanuele de; McGrath, John A.

doi:10.1016/j.jid.2018.05.017

Cited by 39 publications

(45 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While a few gene expression studies have been performed, the majority focused on specific genes or limited microarray studies (25)(26)(27)(28)(29)(30)(31)(32). Furthermore, these studies did not entirely characterize the inflammatory profile of keloids.…”

Section: Introductionmentioning

confidence: 99%

RNA Sequencing Keloid Transcriptome Associates Keloids With Th2, Th1, Th17/Th22, and JAK3-Skewing

Duca

Espino

et al. 2020

Front. Immunol.

View full text Add to dashboard Cite

Keloids are disfiguring, fibroproliferative growths and their pathogenesis remains unclear, inhibiting therapeutic development. Available treatment options have limited efficacy and harbor safety concerns. Thus, there is a great need to clarify keloid pathomechanisms that may lead to novel treatments. In this study, we aimed to elucidate the profile of lesional and non-lesional keloid skin compared to normal skin. We performed gene (RNAseq, qRT-PCR) and protein (immunohistochemistry) expression analyses on biopsy specimens obtained from lesional and non-lesional skin of African American (AA) keloid patients compared to healthy skin from AA controls. Fold-change≥2 and false-discovery rate (FDR)<0.05 was used to define significance. We found that lesional versus normal skin showed significant up-regulation of markers of T-cell activation/migration (ICOS, CCR7), Th2- (IL-4R, CCL11, TNFSF4/OX40L), Th1- (CXCL9/CXCL10/CXCL11), Th17/Th22- (CCL20, S100As) pathways, and JAK/STAT-signaling (JAK3) (false-discovery rate [FDR]<0.05). Non-lesional skin also exhibited similar trends. We observed increased cellular infiltrates in keloid tissues, including T-cells, dendritic cells, mast cells, as well as greater IL-4rα+, CCR9+, and periostin+ immunostaining. In sum, comprehensive molecular profiling demonstrated that both lesional and non-lesional skin show significant immune alternations, and particularly Th2 and JAK3 expression. This advocates for the investigation of novel treatments targeting the Th2 axis and/or JAK/STAT-signaling in keloid patients.

show abstract

Section: Introductionmentioning

confidence: 99%

RNA Sequencing Keloid Transcriptome Associates Keloids With Th2, Th1, Th17/Th22, and JAK3-Skewing

Duca

Espino

et al. 2020

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…24 circRNAs act as a miRNA molecular sponge to regulate the functions of miRNAs. In addition, in the study by Onoufriadis et al, 25 gene association network analysis was also performed to further classify the differentially expressed genes from the RNA-Seq dataset according to reactome pathway terms and correlated expression values among them. It demonstrated a divergent average expression profile of cytokine signaling genes between keloid-prone and healthy individuals during wound healing.…”

Section: Discussionmentioning

confidence: 99%

“…It demonstrated a divergent average expression profile of cytokine signaling genes between keloid-prone and healthy individuals during wound healing. 25 In consequence, it is key and feasible to better understand circRNAs and to construct lncRNA-miRNA-mRNA network, to explore the specific pathogenesis of keloid.…”

Section: Discussionmentioning

confidence: 99%

Expression Profiles of lncRNAs and circRNAs in Keloid

Wang

Xiao

et al. 2019

Plastic and Reconstructive Surgery - Global Open

View full text Add to dashboard Cite

show abstract

“…Such noncoding small RNA molecules play an important role in processes including biological development, metabolism, differentiation, proliferation, and apoptosis. Previous studies have indicated that abnormal expression of miRNAs can cause disease and even cancer, as certain miRNAs function similarly to tumour suppressor genes [12, 13]. Keloids are a type of solid tumour and, in recent years, researchers have focused on the effect of miRNAs on keloid development.…”

Section: Discussionmentioning

confidence: 99%

The Differential Expression of miRNAs and a Preliminary Study on the Mechanism of miR-194-3p in Keloids

Guo

Chang

et al. 2019

BioMed Research International

View full text Add to dashboard Cite

The aim of this study was to detect abnormally expressed microRNA (miRNA) in keloids and to study their functions. The differential expression of miRNAs in keloids and normal tissue was detected by gene microarray. MiRNA expression was verified by real-time PCR. A luciferase reporter gene assay, western blot, and real-time PCR were used to detect the effect of miR-194-3p on RUNX2. An MTT assay and a transwell assay were used to detect the effect of miR-194-3p in both primary cultured fibroblasts and HKF cells. Related proteins were analysed by western blot and real-time PCR. The expression of miR-194-3p was lower in keloids, and MiR-194-3p was shown to target RUNX2 directly. MiR-194-3p inhibited the proliferation and migration of fibroblasts through the inhibition of CDK4 and MMP2. MiR-194-3p and RUNX2 may become new targets for the prevention and treatment of keloids.

show abstract

Time Series Integrative Analysis of RNA Sequencing and MicroRNA Expression Data Reveals Key Biologic Wound Healing Pathways in Keloid-Prone Individuals

Cited by 39 publications

References 10 publications

RNA Sequencing Keloid Transcriptome Associates Keloids With Th2, Th1, Th17/Th22, and JAK3-Skewing

RNA Sequencing Keloid Transcriptome Associates Keloids With Th2, Th1, Th17/Th22, and JAK3-Skewing

Expression Profiles of lncRNAs and circRNAs in Keloid

The Differential Expression of miRNAs and a Preliminary Study on the Mechanism of miR-194-3p in Keloids

Contact Info

Product

Resources

About