TY - JOUR
T1 - ABCG2 confers promotion in gastric cancer through modulating downstream CRKL in vitro combining with biostatistics mining
AU - Wang, Junqing
AU - Zhou, Yunyun
AU - Wang, Lu
AU - Chen, Xuehua
AU - Zhu, Zhenggang
N1 - 1949-2553 Wang, Junqing Yunyun, Zhou Wang, Lu Chen, Xuehua Zhu, Zhenggang Journal Article United States 2016/12/29 Oncotarget. 2017 Jan 17;8(3):5256-5267. doi: 10.18632/oncotarget.14128.
PY - 2017
Y1 - 2017
N2 - ABCG2, member of ATP-binding cassette (ABC) transporter family, is known as crucial regulator related to multi-drug resistance in human tumors and has recently been putatively studied as human carcinoma cell biomarker. While, effects of ABCG2 on human gastric cancer (GC) has not been illustrated thoroughly. In this study, by applying biostatistics mining methods, we observed that ABCG2 is frequently aberrantly expressed in GC patients through exploring dataset of GSE19826 in NCBI GEO database. Contemporary, extreme up-regulation of ABCG2 was discovered in both GC specimens and cell lines of our center, from which we observed high level of ABCG2 associated with GC clinicopathologic features and poor outcomes. Depletion of ABCG2 in MKN-45 GC cells, the cell proliferation was significantly impacted along with cell cycle arrest, and cell apoptosis was induced. Interestingly, combined with data mining of NCBI database, CRKL, a pivotal GC promoter, presents a significant positive correlation with ABCG2. And the expression of CRKL in GC cells was obviously affected through ABCG2 depletion. Simultaneously, over-expression of CRKL in MKN-45 cells significantly rescued most of the phenotypes induced by ABCG2 depletion. Thus, we suggest that ABCG2 is a potential biomarker and target upstream CRKL, which could be further studied for GC diagnosis and therapeutic treatment.
AB - ABCG2, member of ATP-binding cassette (ABC) transporter family, is known as crucial regulator related to multi-drug resistance in human tumors and has recently been putatively studied as human carcinoma cell biomarker. While, effects of ABCG2 on human gastric cancer (GC) has not been illustrated thoroughly. In this study, by applying biostatistics mining methods, we observed that ABCG2 is frequently aberrantly expressed in GC patients through exploring dataset of GSE19826 in NCBI GEO database. Contemporary, extreme up-regulation of ABCG2 was discovered in both GC specimens and cell lines of our center, from which we observed high level of ABCG2 associated with GC clinicopathologic features and poor outcomes. Depletion of ABCG2 in MKN-45 GC cells, the cell proliferation was significantly impacted along with cell cycle arrest, and cell apoptosis was induced. Interestingly, combined with data mining of NCBI database, CRKL, a pivotal GC promoter, presents a significant positive correlation with ABCG2. And the expression of CRKL in GC cells was obviously affected through ABCG2 depletion. Simultaneously, over-expression of CRKL in MKN-45 cells significantly rescued most of the phenotypes induced by ABCG2 depletion. Thus, we suggest that ABCG2 is a potential biomarker and target upstream CRKL, which could be further studied for GC diagnosis and therapeutic treatment.
KW - ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics
KW - Adaptor Proteins, Signal Transducing/metabolism
KW - Biostatistics
KW - Cell Line, Tumor
KW - Cell Proliferation
KW - Computational Biology/methods
KW - Data Mining
KW - Databases, Genetic
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - In Vitro Techniques
KW - Neoplasm Proteins/genetics
KW - Nuclear Proteins/metabolism
KW - Stomach Neoplasms/genetics
KW - Up-Regulation
UR - http://www.scopus.com/inward/record.url?scp=85011965294&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.14128
DO - 10.18632/oncotarget.14128
M3 - Article
C2 - 28029654
SN - 1949-2553
VL - 8
SP - 5256
EP - 5267
JO - Oncotarget
JF - Oncotarget
IS - 3
ER -