scholarly journals Weighted gene coexpression network and experimental analyses identify lncRNA SPRR2C as a regulator of the IL-22-stimulated HaCaT cell phenotype through the miR-330/STAT1/S100A7 axis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Meijunzi Luo ◽  
Pan Huang ◽  
Yi Pan ◽  
Zhu Zhu ◽  
Rong Zhou ◽  
...  

AbstractPsoriasis is a chronic inflammatory disease of the skin with highly complex pathogenesis. In this study, we identified lncRNA SPRR2C (small proline-rich protein 2C) as a hub gene with a critical effect on the pathogenesis of psoriasis and response to treatment using both weighted gene coexpression network analysis (WGCNA) and differential expression analysis. SPRR2C expression was significantly upregulated in both psoriatic lesion samples and HaCaT cell lines in response to IL-22 treatment. After SPRR2C knockdown, IL-22-induced suppression of HaCaT proliferation, changes in the KRT5/14/1/10 protein levels, and suppression of the IL-1β, IL-6, and TNF-α mRNA levels were dramatically reversed. In the coexpression network with SPRR2C based on GSE114286, miR-330 was significantly negatively correlated with SPRR2C, while STAT1 and S100A7 were positively correlated with SPRR2C. By binding to miR-330, SPRR2C competed with STAT1 and S100A7 to counteract miR-330-mediated suppression of STAT1 and S100A7. MiR-330 overexpression also reversed the IL-22-induced changes in HaCaT cell lines; in response to IL-22 treatment, miR-330 inhibition significantly attenuated the effects of SPRR2C knockdown. STAT1 and S100A7 expression was significantly upregulated in psoriatic lesion samples. The expression of miR-330 had a negative correlation with the expression of SPRR2C, while the expression of SPRR2C had a positive correlation with the expression of STAT1 and S100A7. Thus, SPRR2C modulates the IL-22-stimulated HaCaT cell phenotype through the miR-330/STAT1/S100A7 axis. WGCNA might uncover additional biological pathways that are crucial in the pathogenesis and response to the treatment of psoriasis.

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Ming Yi ◽  
Tianye Li ◽  
Shuang Qin ◽  
Shengnan Yu ◽  
Qian Chu ◽  
...  

Lung adenocarcinoma is the most frequently diagnosed subtype of nonsmall cell lung cancer. The molecular mechanisms of the initiation and progression of lung adenocarcinoma remain to be further determined. This study aimed to screen genes related to the progression of lung adenocarcinoma. By weighted gene coexpression network analysis (WGCNA), we constructed a free-scale gene coexpression network to evaluate the correlations between multiple gene sets and patients’ clinical traits, then further identify predictive biomarkers. GSE11969 was obtained from the Gene Expression Omnibus (GEO) database which contained the gene expression data of 90 lung adenocarcinoma patients. Data of the Cancer Genome Atlas (TCGA) were employed as the validation cohort. After the average linkage hierarchical clustering, a total of 9 modules were generated. In the clinical significant module (R = 0.44, P<0.0001), we identified 29 network hub genes. Subsequent verification in the TCGA database showed that 11 hub genes (ANLN, CDCA5, FLJ21924, LMNB1, MAD2L1, RACGAP1, RFC4, SNRPD1, TOP2A, TTK, and ZWINT) were significantly associated with poor survival data of lung adenocarcinomas. Besides, the results of receiver operating characteristic curves indicated that the mRNA levels of this group of genes exhibited high specificity and sensitivity to distinguish malignant lesions from nonmalignant tissues. Apart from mRNA levels, we found that the protein abundances of these 11 genes were remarkably upregulated in lung adenocarcinomas compared with normal tissues. In conclusion, by the WGCNA method, a panel of 11 genes were identified as predictive biomarkers for tumorigenesis and poor prognosis of lung adenocarcinomas.


2021 ◽  
Vol 11 (19) ◽  
pp. 9244
Author(s):  
Monika Kalinowska ◽  
Hanna Lewandowska ◽  
Marek Pruszyński ◽  
Grzegorz Świderski ◽  
Ewelina Gołębiewska ◽  
...  

In this study a cobalt(II) complex of quercetin was synthetized in the solid state with the general formula Co(C15H9O7)2∙2H2O. The FT-IR, elemental analysis, and UV/Vis methods were used to study the composition of the complex in a solid state and in a water solution. The anti-/pro-oxidant activity of quercetin and the Co(II) complex was studied by means of spectrophotometric DPPH (2,2-diphenyl-1-picrylhydrazyl), FRAP (ferric reducing antioxidant activity) and Trolox oxidation assays. The cytotoxicity of quercetin and Co(II)-quercetin complex in HaCat cell lines was then established.


2019 ◽  
Vol 49 (10) ◽  
pp. 1195-1206 ◽  
Author(s):  
Aiping Tian ◽  
Ke Pu ◽  
Boxuan Li ◽  
Min Li ◽  
Xiaoguang Liu ◽  
...  

Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 699 ◽  
Author(s):  
Wenrong Yao ◽  
Ying Guo ◽  
Xi Qin ◽  
Lei Yu ◽  
Xinchang Shi ◽  
...  

The therapeutic recombinant human keratinocyte growth factor 1 (rhKGF-1) was approved by the FDA for oral mucositis resulting from hematopoietic stem cell transplantation for hematological malignancies in 2004. However, no recommended bioassay for rhKGF-1 bioactivity has been recorded in the U.S. Pharmacopoeia. In this study, we developed an rhKGF-1-dependent bioassay for determining rhKGF-1 bioactivity based on HEK293 and HaCat cell lines that stably expressed the luciferase reporter driven by the serum response element (SRE) and human fibroblast growth factor receptor (FGFR2) IIIb. A good responsiveness to rhKGF-1 and rhKGF-2 shared by target HEK293/HaCat cell lines was demonstrated. Our stringent validation was completely focused on specificity, linearity, accuracy, precision, and robustness according to the International Council for Harmonization (ICH) Q2 (R1) guidelines, AAPS/FDA Bioanalytical Workshop and the Chinese Pharmacopoeia. We confirmed the reliability of the method in determining rhKGF bioactivity. The validated method is highly timesaving, sensitive, and simple, and is especially valuable for providing information for quality control during the manufacture, research, and development of therapeutic rhKGF.


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