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

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

Polymorphisms of xenobiotic-metabolizing and transporter genes and the risk of gastric and colorectal cancer in an admixed population of Brazil.

“…Therefore, the assessment of differential expressions of BRCP may lead the scientific community to create a new method to evaluate progression, metastasis and to predict therapeutic response of colorectal cancer. The results also corroborate with the findings of Wang and colleagues, who, through an in vitro experiment, demonstrated that the ABCG2 gene shows dysregulated expression in GC tissues and cells [28]. In this study, the high expression of ABCG2/BRCP was correlated with advanced stages and poor prognosis of GC.…”

Pseudogene AKR1B10P1 enhances tumorigenicity and regulates epithelial‐mesenchymal transition in hepatocellular carcinoma via stabilizing SOX4

“…The cell proliferation curves were plotted. Methods above refer to our previous research 19 . The aforementioned cells were treated in steps with ethanol fixation, RNase A treatment and propidium iodide staining.…”

Effect of sodium butyrate on ABC transporters in lung cancer A549 and colorectal cancer HCT116 cells

“…It has been revealed that MRP1-3 lead to resistance to hydrophobic and anionic compounds, including several natural compounds, whereas MRP4, MRP5 and MRP8 efflux cyclic nucleotides (13,14). BCRP, a ubiquitous ABC transporter, has been shown to transport nucleoside drugs and nucleoside-monophosphate derivatives of clinically relevant nucleoside drugs (15,16). Moreover, these ABC transporters are highly expressed in various human cancer types and are closely associated with poor prognosis (17,18).…”