Transcriptome wide analysis of long non-coding RNA-associated ceRNA regulatory circuits in psoriasis.
Jingxia LinXuefei LiFangfei ZhangLei ZhuYong-Feng ChenPublished in: Journal of cellular and molecular medicine (2021)
Long non-coding RNAs (lncRNAs) play critical roles in regulating immune-associated diseases and chronic inflammatory disorders. Here, we found that lncRNAs involve in the pathogenesis of psoriasis through integrative analysis of RNA-seq data sets from a psoriasis cohort. Then, lncRNA-protein-coding genes (PCGs) co-expression network analysis demonstrated that lncRNAs extensively interact with IFN-γ signalling pathway-associated genes. Further, we validated 3 lncRNAs associate with IFN-γ signalling pathway activation upon IFN-γ stimulated in HaCaT cells, and loss of function experiments indicate their functional roles in the activation of inflammatory cytokine genes. Additionally, microRNA target screening analysis showed that lncRNAs may regulate JAK/STAT pathway activity through complete endogenous RNA (ceRNA) mechanism. Further experimental validation of PRKCQ-AS1/STAT1/miR-545-5p regulatory circuitry showed that lncRNAs regulate the expression of JAK/STAT signalling pathway genes through competing for miR-545-5p. In summary, our results demonstrated that dysregulation of lncRNA-JAK/STAT pathway axis promotes the inflammation level in psoriasis and thus provide potential therapeutic targets for psoriasis treatments.
Keyphrases
- long non coding rna
- network analysis
- poor prognosis
- genome wide identification
- genome wide analysis
- rna seq
- transcription factor
- genome wide
- single cell
- oxidative stress
- dendritic cells
- immune response
- bioinformatics analysis
- atopic dermatitis
- gene expression
- induced apoptosis
- dna methylation
- signaling pathway
- machine learning
- big data
- binding protein
- cell proliferation
- multidrug resistant
- small molecule
- data analysis
- deep learning
- artificial intelligence