Biology subjects

Wan, Q.

Publications and source records attributed to Wan, Q..

22 records · Page 2Linked to original sources

bioRxiv2020

Single extracellular vesicles protein profiling classifies renal fibrosis stages in mice model

Renal fibrosis is a common consequence of various chronic kidney diseases (CKD), leading to the loss of renal function and even end-stage renal failure. Extracellular vesicles (EVs) were shown to be involved in development of CKD and renal fibrosis. In this study, we induced renal fibrosis in mice model through unilateral ureteral obstruction (UUO) and extracted EVs from the kidney with induced fibrosis. Proximity barcoding assay (PBA) was performed to detect the expression of 112 proteins at individual EVs level for renal fibrosis of Grade I to IV and sham control group as well. The single EVs are classified into subpopulations according to the surface proteomic characteristics. We discovered several EV subpopulations, with presence of ITGAM, ITGA6, CD73, CD13 and ALDH1, increase significantly with development of renal fibrosis. These findings indicate that besides protein expression, proteomic fingerprints of single EVs can be potential biomarkers for surveillance of CKD and renal fibrosis.

molecular biology↗

bioRxiv2018

KGF induces podosome formation via integrin-Erk1/2 signaling in human immortalized oral epithelial cells

Our recent study established the role of integrins in KGF-induced oral epithelial adhesion and rete peg elongation. However, how extracellular matrix remodeling cooperates with the increased epithelial adhesion during rete peg elongation has yet to be determined. Podosomes are cell-matrix contact structures that combine several abilities, including adhesion and matrix degradation. In the present study, we identified podosome formation at the ventral side of human immortalized oral epithelial cells (HIOECs) upon KGF treatment. Moreover, podosomal components colocalized with the F-actin-cortactin complex and matrix degradation assays demonstrated the ability of the F-actin-cortactin complex to degrade matrix. Inhibition both of integrin subunits {beta}4 and {beta}l with specific blocking antibodies and inhibition of Erk1/2 abrogated the KGF-induced podosome formation. Notably, knockdown of integrin subunits {beta}4 and {beta}l with specific siRNA downregulated the phosphorylation levels of Erk1/2. In contrast, inhibition of both Erk1/2 could upregulate the expression of integrin subunits {beta}4 and {beta}1. These results demonstrate that KGF induces podosome formation via integrin-Erk1/2 signaling in HIOECs, suggesting a novel mechanism by which integrins enhance oral epithelial adhesion and rete peg elongation.\n\nSummary StatementHuman immortalized oral epithelial cells can form podosomes after stimulation with KGF during which integrin-Erk1/2 signaling play essential roles.

cell biology↗

bioRxiv2018

Identification of Key Differentially Expressed MicroRNAs in Cancer Patients Through Pan-cancer Analysis

A number of microRNAs (miRNAs) functioning in gene silencing have been associated with cancer progression. However, common expression patterns of abnormally expressed miRNAs and their potential roles in multiple cancer types have not yet been evaluated. To minimize the difference of patients, we collected miRNA sequencing data of 575 patients with tumor and adjacent non-tumorous tissues from 14 cancer types from The Cancer Genome Atlas (TCGA), and performed differential expression analysis using DESeq2 and edgeR. The results showed that cancer types can be grouped based on the distribution of miRNAs with different expression patterns. We found 81 significantly differentially expressed miRNAs (SDEmiRNAs) unique to one of the 14 cancers may affect patient survival rate, and 21 key SDEmiRNAs (nine overexpressed and 12 under-expressed) associated with at least eight cancers and enriched in more than 60% of patients per cancer, including four newly identified SDEmiRNAs (hsa-mir-4746, hsa-mir-3648, hsa-mir-3687, and hsa-mir-1269a). The downstream effect of these 21 SDEmiRNAs on cellular functions was evaluated through enrichment and pathway analysis of 7,186 protein-coding gene targets from literature mining with known differential expression profiles in cancers. It enables identification of their functional similarity in cell proliferation control across a wide range of cancers and to build common regulatory networks over cancer-related pathways. This is validated by construction of a regulatory network in PI3K pathway. This study provides evidence of the value of further analysis on SDEmiRNAs as potential biomarkers and therapeutic targets for cancer diagnosis and treatment.

bioinformatics↗

bioRxiv2017

Separating an allele associated with late flowering and slow maturation of Arabidopsis thaliana from population structure

Genome-wide association analysis is a powerful tool to identify genomic loci underlying complex traits. However, the application in natural populations comes with challenges, especially power loss due to population stratification. Here, we introduce a bivariate analysis approach to a GWAS dataset of Arabidopsis thaliana. We demonstrate the efficiency of double-phenotype analysisto uncover hidden genetic loci masked by population structure via a series of simulations. In real data analysis, acommon allele, strongly confounded with population structure, is discovered to be associated with late flowering and slow maturation of the plant. The discovered genetic effect on flowering time is further replicated in independent datasets. Using Mendelian randomization analysis based on summary statistics from our GWAS and expression QTL scans, we predicted and replicated a candidate gene AT1G11560 that potentially causes this association. Further analysis indicates that this locusis co-selected with flowering-time-related genes. The discovered pleiotropic genotypephenotype map provides new insights into understanding the genetic correlation of complex traits.

genetics↗