TY - JOUR
T1 - An integrated pan-cancer analysis and structure-based virtual screening of GPR15
AU - Wang, Yanjing
AU - Wang, Xiangeng
AU - Xiong, Yi
AU - Li, Cheng Dong
AU - Xu, Qin
AU - Shen, Lu
AU - Kaushik, Aman Chandra
AU - Wei, Dong Qing
N1 - Funding Information:
This work was supported by the funding from National Key Research Program (Contract No.2016YFA0501703), National Natural Science Foundation of China (Grant No. 31601074, 61872094, 61832019), and Shanghai Jiao Tong University School of Medicine (Contract No. YG2017ZD14). We thank all members of the laboratory for useful discussion.
Funding Information:
Funding: This work was supported by the funding from National Key Research Program (Contract No.2016YFA0501703), National Natural Science Foundation of China (Grant No. 31601074, 61872094, 61832019), and Shanghai Jiao Tong University School of Medicine (Contract No. YG2017ZD14).
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/12/2
Y1 - 2019/12/2
N2 - G protein-coupled receptor 15 (GPR15, also known as BOB) is an extensively studied orphan G protein-coupled receptors (GPCRs) involving human immunodeficiency virus (HIV) infection, colonic inflammation, and smoking-related diseases. Recently, GPR15 was deorphanized and its corresponding natural ligand demonstrated an ability to inhibit cancer cell growth. However, no study reported the potential role of GPR15 in a pan-cancer manner. Using large-scale publicly available data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we found that GPR15 expression is significantly lower in colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) than in normal tissues. Among 33 cancer types, GPR15 expression was significantly positively correlated with the prognoses of COAD, neck squamous carcinoma (HNSC), and lung adenocarcinoma (LUAD) and significantly negatively correlated with stomach adenocarcinoma (STAD). This study also revealed that commonly upregulated gene sets in the high GPR15 expression group (stratified via median) of COAD, HNSC, LUAD, and STAD are enriched in immune systems, indicating that GPR15 might be considered as a potential target for cancer immunotherapy. Furthermore, we modelled the 3D structure of GPR15 and conducted structure-based virtual screening. The top eight hit compounds were screened and then subjected to molecular dynamics (MD) simulation for stability analysis. Our study provides novel insights into the role of GPR15 in a pan-cancer manner and discovered a potential hit compound for GPR15 antagonists.
AB - G protein-coupled receptor 15 (GPR15, also known as BOB) is an extensively studied orphan G protein-coupled receptors (GPCRs) involving human immunodeficiency virus (HIV) infection, colonic inflammation, and smoking-related diseases. Recently, GPR15 was deorphanized and its corresponding natural ligand demonstrated an ability to inhibit cancer cell growth. However, no study reported the potential role of GPR15 in a pan-cancer manner. Using large-scale publicly available data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we found that GPR15 expression is significantly lower in colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) than in normal tissues. Among 33 cancer types, GPR15 expression was significantly positively correlated with the prognoses of COAD, neck squamous carcinoma (HNSC), and lung adenocarcinoma (LUAD) and significantly negatively correlated with stomach adenocarcinoma (STAD). This study also revealed that commonly upregulated gene sets in the high GPR15 expression group (stratified via median) of COAD, HNSC, LUAD, and STAD are enriched in immune systems, indicating that GPR15 might be considered as a potential target for cancer immunotherapy. Furthermore, we modelled the 3D structure of GPR15 and conducted structure-based virtual screening. The top eight hit compounds were screened and then subjected to molecular dynamics (MD) simulation for stability analysis. Our study provides novel insights into the role of GPR15 in a pan-cancer manner and discovered a potential hit compound for GPR15 antagonists.
KW - Cancer immunity
KW - Differential gene expression
KW - Orphan receptor GPR15/BOB
KW - Pan-cancer
KW - Prognosis
KW - TCGA
KW - Virtual screening
UR - http://www.scopus.com/inward/record.url?scp=85077286472&partnerID=8YFLogxK
U2 - 10.3390/ijms20246226
DO - 10.3390/ijms20246226
M3 - Article
C2 - 31835584
AN - SCOPUS:85077286472
SN - 1661-6596
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 24
M1 - 6226
ER -
