ABCG2 confers promotion in gastric cancer through modulating downstream CRKL in vitro combining with biostatistics mining

摘要

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 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