Abstract
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
Highlights
Gastric cancer (GC) is one of the most common human carcinomas around the world, contributing to 10% newly diagnosed cases per year with relatively high mortality in patients of advanced stages [1]
ABCG2 is a potential regulator of downstream CRKL, and ectopic introduction of CRKL into MKN-45 cells significantly rescues the phenotypes induced by ABCG2 depletion
ABCG2 is up-regulated through NCBI GEO database mining and highly expressed in gastric cancer (GC) tissues
Summary
Gastric cancer (GC) is one of the most common human carcinomas around the world, contributing to 10% newly diagnosed cases per year with relatively high mortality in patients of advanced stages [1]. ATP-binding cassette subfamily G, member 2 (ABCG2), is a member of the ATP-binding cassette (ABC) transporter family It was firstly discovered in a process involving in multidrug resistance (MDR) from doxorubicin-resistant human MCF-7 breast cancer cells [4,5,6], and was reported to induce sorafenib resistance in hepatocellular carcinoma (HCC) cells [7]. ABCG2 has been studied as a potential marker of cancer stem cells (CSCs) in diverse human malignances, associated with tumor initiation, maintenance, relapse, metastasis and MDR, which suggests ABCG2 a hopeful target in cancer treatment [9,10,11,12,13]. We firstly mined and discovered aberrant expression of ABCG2 in GC patients from NCBI database, which directed us to conduct further investigation in both GC tumor tissues and cell lines. What we discovered here indicates ABCG2 as a promoter in GC cells through regulating CRKL
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