ABCG2 confers promotion in gastric cancer through modulating downstream CRKL in vitro combining with biostatistics
Junqing Wang1,2,3, Zhou Yunyun4, Lu Wang5
1Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 20025, People's Republic of China.
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.
Insights
ABCG2 transporter is highly expressed in gastric cancer (GC), promoting tumor growth and poor outcomes. Targeting ABCG2 may offer new therapeutic strategies by influencing CRKL, a key GC promoter.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- ATP-binding cassette (ABC) transporter G2 (ABCG2) is implicated in multi-drug resistance and cancer progression.
- The role of ABCG2 in human gastric cancer (GC) pathogenesis remains incompletely understood.
Purpose of the Study:
- To investigate the expression, clinical significance, and functional role of ABCG2 in gastric cancer.
- To explore the relationship between ABCG2 and CRKL in GC progression.
Main Methods:
- Bioinformatic analysis of the GSE19826 dataset from the NCBI GEO database.
- Expression analysis in GC specimens and cell lines.
- Functional studies involving ABCG2 depletion in MKN-45 GC cells.
- CRKL expression analysis and rescue experiments.
Main Results:
- ABCG2 is frequently aberrantly expressed and significantly upregulated in GC patients and cell lines.
- High ABCG2 levels correlate with adverse clinicopathologic features and poor prognosis in GC.
- ABCG2 depletion inhibits GC cell proliferation, induces cell cycle arrest, and promotes apoptosis.
- A positive correlation between ABCG2 and CRKL was identified, with CRKL expression affected by ABCG2 levels.
Conclusions:
- ABCG2 acts as a potential biomarker and therapeutic target in gastric cancer.
- ABCG2 exerts its oncogenic effects, at least partly, by regulating the expression of CRKL.
- Targeting the ABCG2/CRKL axis may represent a promising strategy for GC diagnosis and treatment.
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